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retinoic acid receptor
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  retinoic acid receptor
Our previous data indicated that the combination of ligands for peroxisome proliferator-activated receptor γ (PPARγ) and retinoic acid receptor (RAR) induces apoptosis of breast cancer cells in vitro and in a murine model.
      
Using monoclonal antibodies for retinoic acid receptor alpha (RARα), we found nuclear staining in melanomas and lung carcinomas metastatic to brain and only rarely in gliomas.
      
Paucity of Retinoic Acid Receptor Alpha (RARα) Nuclear Immunostaining in Gliomas and Inability of Retinoic Acid to Influence Neu
      
CNS-1 was immunoreactive for glial fibrillary acidic protein, S100 protein, vimentin, neural cell adhesion molecule, retinoic acid receptor α, intercellular adhesion molecule, and neuron specific enolase.
      
RA was previously shown to down-regulate the steady state levels of retinoic acid receptor α (RARα) and retinoid X receptor α (RXRα) in primary brown adipocytes differentiated in culture.
      
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AIM To study the molecular mechanisms of retinoic acid (RA) regulating the expression of collagen produced by lung fibroblasts in vivo. METHOD Rats were divided into control, fibrosis and treatment groups and killed at d 28 after bleomycin administration. The lungs were dissected and cultured for lung fibroblasts. The primarily cultured fibroblasts from different groups were used for determination of levels of procollagen α 1(I) mRNA by Northern blot and the content of collagen protein...

AIM To study the molecular mechanisms of retinoic acid (RA) regulating the expression of collagen produced by lung fibroblasts in vivo. METHOD Rats were divided into control, fibrosis and treatment groups and killed at d 28 after bleomycin administration. The lungs were dissected and cultured for lung fibroblasts. The primarily cultured fibroblasts from different groups were used for determination of levels of procollagen α 1(I) mRNA by Northern blot and the content of collagen protein by [ 3H] proline incorporation assay. The nuclear protein of fibroblasts was also extracted and used for measurement of AP 1 activity by Gel mobility shift assay. The mRNA levels of retinoic acid receptors were determined by RT PCR. RESULT RA induced the expression of RXRα mRNA and down regulated the AP 1 activity which was enhanced in the fibroblasts from fibrosis groups. RA also greatly reduced both the levels procollagen α 1(I) mRNA and the content of collagen protein which were obviously increased in the fibroblasts from rats of fibrosis group. CONCLUSION The enhanced AP 1 activity may play an important role in mediating the overexpression of collagen protein by fibroblasts from fibrosis group. RA reduces the level of procollagen α 1(I) mRNA of fibroblasts by inducing the expression of RXRα which is known to be able to antagonize AP 1 activity.

目的 研究维甲酸 (RA)对肺纤维化大鼠肺成纤维细胞胶原表达的影响及机制。方法 正常组、纤维化组和RA治疗组 3组大鼠分别于肺纤维化模型制备后d 2 8处死 ,取肺组织进行肺成纤维细胞的原代培养。用Northernblot方法检测原代培养肺成纤维细胞前胶原α1(Ⅰ )mRNA表达 ,[3 H] 脯氨酸参入法测定胶原蛋白合成 ,凝胶迁移率法检测核因子AP 1活性 ,RT PCR方法测维甲酸受体的mRNA表达。结果 RA可诱导肺成纤维细胞RXRαmRNA的表达 ,使肺纤维化时增高的AP 1活性下调 ,并抑制前胶原α1(Ⅰ )mRNA表达及胶原蛋白合成。结论 肺纤维化时肺成纤维细胞AP 1活性增高可能是导致胶原过度表达的重要机制。RA可能通过诱导肺成纤维细胞RXRα的表达使增高的AP 1活性得以抑制 ,从而下调胶原基因的表达。

Aim To screen new drug for the treatment of acute promyelocytic leukemia, psoriasis and acne, high-throughput drug screening cell models marked by green fluorescent protein (GFP) have been established. Methods Eight repeats of retinoic acid response element (RARE) were synthesized and cloned into a GFP expression vector. This construct was stably transfected into cells in vitro. Stable and sensitive cell clones with high copy numbers of RARE were selected by retinoic acid (RA) using fluorescence-activated cell...

Aim To screen new drug for the treatment of acute promyelocytic leukemia, psoriasis and acne, high-throughput drug screening cell models marked by green fluorescent protein (GFP) have been established. Methods Eight repeats of retinoic acid response element (RARE) were synthesized and cloned into a GFP expression vector. This construct was stably transfected into cells in vitro. Stable and sensitive cell clones with high copy numbers of RARE were selected by retinoic acid (RA) using fluorescence-activated cell sorting (FACS). Results A cell line has been chosen to be high-throughput drug screening cell model. This model was shown with low background, high sensitive and good reproducibility, and was convenient and inexpensive. Conclusion This drug screening cell model can be used for retinoic acid receptor target high-throughput drug screening.

目的建立绿色荧光蛋白(GFP)标记的以维甲酸受体为靶点的高通量药物筛选细胞模型,用于筛选治疗急性早幼粒细胞白血病(APL)、银屑病、痤疮以及肿瘤的新型药物。方法用分子生物学的方法,构建含有8个串连维甲酸受体应答元件(RARE)并连接报告基因E-GFP的重组载体。将体外培养的细胞株用该重组载体进行稳定转染,然后进行单克隆培养,最终挑选出敏感、高效、稳定表达的单克隆细胞,用于筛选针对维甲酸受体的小分子有机药物。结果建立了高效的药物筛选细胞模型。此模型筛选方法简便,适用范围广,灵敏度高,结果稳定。结论挑选出的细胞株作为药物筛选模型可用于大规模高通量药物筛选。

The recent researches on retinoids with anticancer activity were reviewed.And future trends in the research of retinoids as anticancer medicines were also presented.Retinoids regulate the gene expression by activating two kinds of receptors: retinoic acid receptor and retinoid x receptor,and have protective effects against the development of certain types of cancer.Some retinoids may become the promising candidates of clinical anticancer medicines.

综述具有抗肿瘤活性的维甲酸类化合物的研究现状,并展望其今后的研究动向。维甲酸类化合物通过激活其核受体蛋白来调控核基因的表达,产生抗肿瘤作用,其中一些有望成为临床抗肿瘤药物。

 
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