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A comparative study of phosphate-activated glutaminase activity has been conducted in some normal and tumour tissues. It was found that:(1) There was a wide range of difference in the glutaminase activity among the tumours so far investigated, which was however not as wide as that observed in the normal tissues. The highest level of glutaminase activity was found in the transplanted thymolymphosarcoma, which was about seven times higher than that in the normal thymus.(2) During the growth of transplanted solid...

A comparative study of phosphate-activated glutaminase activity has been conducted in some normal and tumour tissues. It was found that:(1) There was a wide range of difference in the glutaminase activity among the tumours so far investigated, which was however not as wide as that observed in the normal tissues. The highest level of glutaminase activity was found in the transplanted thymolymphosarcoma, which was about seven times higher than that in the normal thymus.(2) During the growth of transplanted solid tumours, the glutaminase activity was found to vary with the weight of tumour tissue. An approximate parallelism between the increase in glutaminase activity and the weight of tumour has been observed in some, but not all of the tumours so far studied.(3) The enzyme activity in the regenerating rat liver was lower than that in the normal liver.(4) The possible significance of glutaminase to the growth of some tumours has been discussed.

(1) 本实验比较了一些正常组织与癌瘤组织中谷氨酰胺酶活性。结果发现移植性癌瘤的酶活性以淋巴肉瘤最。肿瘤间酶活性的变动范围不如正常组织间的变动范围大。诱发性淋巴肉瘤的酶活性较其来源组织为,但皮肤癌则较正常表皮低。(2) 在肿瘤生长过程中,谷氨酰胺酶活性随肿瘤的重量而有所变化,如艾氏腹水癌(实质型)、脑瘤22、胸腺淋巴肉瘤等的谷氨酰胺酶活性有随肿瘤生长而升的趋势,但这并不是肿瘤的一般规律,如脑瘤53、Walker癌、肉瘤180等则无此现象。(3) 再生肝的谷氨酰胺酶活性较正常肝低。(4) 讨论了谷氨酰胺酶与某些肿瘤生长的可能关系。

In the 3'-MeDAB induced liver tumour, it was found that the activities of glucoses-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase and dipeptidases were higher than those in the normal liver, while the activities of glutamic dehydrogenase, glutaminase(phosphate-activated), ornithine carbamyl transferase, tryptophan pyrrolase, threonine dehydrase and tyrosine transaminase were lower or even absent.Changes in most enzyme activities were observed in the precancerous stage and the pattern of these changes...

In the 3'-MeDAB induced liver tumour, it was found that the activities of glucoses-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase and dipeptidases were higher than those in the normal liver, while the activities of glutamic dehydrogenase, glutaminase(phosphate-activated), ornithine carbamyl transferase, tryptophan pyrrolase, threonine dehydrase and tyrosine transaminase were lower or even absent.Changes in most enzyme activities were observed in the precancerous stage and the pattern of these changes followed that in the liver tumour. Thus in the course of carcinogenesis, the activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase and dipeptidase(glycylglycine as substrate)increased while those of glutamic dehydrogenase, glutaminase and ornithine carbamyl transferase decreased. However, there was no significant change in the activity of dipeptidase when DL-alanylglycine was used as substrate. Changes in activity of tryptophan pyrrolase and tyrosine transaminase were not pronounced as compared with those of the control. The activity of glutathione reductase in the liver tumour was similar to that of normal liver, but it increased from the 4th to 13th week of feeding of the carcinogen. Threonine dehydrase was remarkably influenced by the nutritive factor of the basal diet so that the effect of 3'-MeDAB on threonine dehydrase could not be observed during carcinogenesis.A comparative study has been made with 2-MeDAB, a non-carcinogenic substance. It had no apparent effect on the above enzymes except that it caused the activity of glutamic dehydrogenase to be higher than that of the control.Further experiments have shown that the specific activities of glutamic dehydrogenase and glutaminase in the mitochondria of liver tumour were lower than those of the control. In the precancerous liver the specific activity of glutaminase in the mitochondria was lower than that of the control, while there was no significant change in the case of glutamic dehydrogenase.From these results together with those from other laboratories a possible biochemical mechanism of the carcinogenesis induced by 3'-MeDAB was proposed(Fig. 12). It was suggested that the change in enzyme activity during carcinogenesis may possibly have resulted from the carcinogen being first metabolized in the liver, leading to a higher activity of the oxidative metabolism of glucose-6-phosphate and exhibiting influences on liver enzymes by the metabolites of 3'-MeDAB through different mechanisms. Consequently there produced an abnormal growth and differentiation of liver cell which became neoplastic with the formation of liver cancer, 2-MeDAB may be metabolized in a different way from that of 3'-MeDAB thus producing different effects on most enzyme activities. It is therefore evident that the specific effect of 3'-MeDAB on the liver enzymesmay be closely related to its property of carcinogenisity.

在3'-MeDAB誘发的肝癌組織中,G-6-PD、6-PGD、二肽酶的活性都較正常肝,而另一些酶如GDH、GMA、OCT、TP、TD、TTA的活性則較正常肝低或甚至測不出来。大多数酶活性都在癌前期即有明显的变化,其变化情况多趋向于癌的特征,如肝癌組織中活性較的酶,在引癌过程中其活性較对照組有升趋势,如G-6-PD、6-PGD、二肽酶(以甘氨酰甘氨酸为底物);肝癌組織中活性降低的酶,在引癌过程中其活性有降低趋势,如GDH、GMA、OCT。但以丙氨酰甘氨酸为底物的二肽酶活性的变化則与对照組基本相似。癌前期TP及TTA活性較对照組都无明显差异。肝癌組織中GSSGR活性与正常肝相似,但在引癌过程中(4—13周)則有升趋势。苏氨酸去水酶受基础食料中营养因素的影响較大,癌前期看不出3'-MeDAB对它的影响。非致癌物,2-MeDAB,除了使GDH活性升外,对上述其他酶活性都无明显的影响。肝癌綫粒体內GMA和GDH比活性都較对照組及正常肝綫粒体为低。癌前期肝綫粒体GMA比活性較对照組显著降低,而GDH比活性則无明显改变。根据本实驗及其他实驗室結果,我們认...

在3'-MeDAB誘发的肝癌組織中,G-6-PD、6-PGD、二肽酶的活性都較正常肝,而另一些酶如GDH、GMA、OCT、TP、TD、TTA的活性則較正常肝低或甚至測不出来。大多数酶活性都在癌前期即有明显的变化,其变化情况多趋向于癌的特征,如肝癌組織中活性較的酶,在引癌过程中其活性較对照組有升趋势,如G-6-PD、6-PGD、二肽酶(以甘氨酰甘氨酸为底物);肝癌組織中活性降低的酶,在引癌过程中其活性有降低趋势,如GDH、GMA、OCT。但以丙氨酰甘氨酸为底物的二肽酶活性的变化則与对照組基本相似。癌前期TP及TTA活性較对照組都无明显差异。肝癌組織中GSSGR活性与正常肝相似,但在引癌过程中(4—13周)則有升趋势。苏氨酸去水酶受基础食料中营养因素的影响較大,癌前期看不出3'-MeDAB对它的影响。非致癌物,2-MeDAB,除了使GDH活性升外,对上述其他酶活性都无明显的影响。肝癌綫粒体內GMA和GDH比活性都較对照組及正常肝綫粒体为低。癌前期肝綫粒体GMA比活性較对照組显著降低,而GDH比活性則无明显改变。根据本实驗及其他实驗室結果,我們认为:3'-MeDAB所引起的肝脏酶活性变化,可能是由于它在肝內进行代謝引起G-6-P旁路代謝的活跃,以及3'-MeDAB代謝产物通过各种不同机制对酶的影响所致。这些酶活性的变化可能导致肝細胞的异常生长和异常分化因而形成肝癌(图12)。非致癌物,2-MeDAB,可能与3'-MeDAB的代謝途径不同,因而产生不同的影响,而3'-MeDAB所产生的特殊影响則可能与其致癌作用有关。

The changes of tyrosine transaminase activity (TAT) and nucleotide 5'-phosphodiesterase activity (5'-NPDase) during foetal development and carcinogenesis in rats and in human beings were observed. Results so far obtained indicate that (1) a higher positive rate of the fastest moving isoenzyme band for 5'-NPDase has been noted in AFP (-) patients with liver cancer, and (2) TAT, 5'-NPDase and AFP may be taken together as good markers for the study of gene expression during liver caroinogenesis and foetal development....

The changes of tyrosine transaminase activity (TAT) and nucleotide 5'-phosphodiesterase activity (5'-NPDase) during foetal development and carcinogenesis in rats and in human beings were observed. Results so far obtained indicate that (1) a higher positive rate of the fastest moving isoenzyme band for 5'-NPDase has been noted in AFP (-) patients with liver cancer, and (2) TAT, 5'-NPDase and AFP may be taken together as good markers for the study of gene expression during liver caroinogenesis and foetal development.

本文测定了大鼠及人体胚胎发育和癌变过程中TAT和5′-NPDase活力变化,所得结果表明: (一)5′-NPDase快速同工酶区带在甲胎蛋白(AFP)阴性肝癌患者血清中阳性率较。(二)TAT,5′-NPDase和AFP也许可作为研究癌、胚以及肝癌癌变过程中基因表达的三个互补生化指标。

 
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