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The Design and Synthesis of a Novel, Orally Active, Selective ETA Antagonist
      
The pharmacokinetics of α- and β-diastereomers of Arteether, a well-known antimalarial drug and its active metabolite dihydroartemisinin (DHA) were studied in Sprague-Dawley rats, Rhesus monkeys and human volunteers.
      
The same compounds were studied using CoMFA for which the molecules were first aligned to a template molecule, which was most active in the series.
      
Among these compounds, 6-benzo[1,3]dioxol-5-yl-4-oxo-hex-5-enoic acid (3) was the most active one.
      
Only 15.33% of the cells was metabolically active at 200 μg/ml methanol extract while 23.57% of the cells was active at 200 μg/ml berberine.
      
Increased inhibitory effect of methanol extracts over berberine demonstrates the occurrence of other cytotoxic principles along with main active principle berberine or other factors enhancing the cytotoxic effect of berberine.
      
Therefore, van der Waals' interactions between acetylcholinesterase and these drugs are stronger than those between butyrylcholinesterase probably due to a small active site gorge and a significant peripheral anionic site for acetylcholinesterase.
      
Compounds 5 and 8 with seven-member C ring were more active than etofylline and caused 100% relaxation of both the histamine and acetycholine pre-contracted guinea pig tracheal chain.
      
Among the nine compounds tested, 5h showed the best selective antiproliferative properties in vitro, being especially active against the human metastatic melanoma cells - inhibition by 93% after 96 h treatment at 10-4 M concentration.
      
The 'active' compounds, which reduced growth of cancer cells to ca.
      
Finally, we applied the model for prediction of a promising new BABQ compound expected to be highly active, and it is seen that our model is in good agreement with the hypothesis in terms of in vitro and in vivo activities.
      
On the basis of preliminary AR inhibitory screening results on 2H-pyridazine-3-one and 6-chloropyridazine derivatives, we embarked on the synthesis of more derivatives to discover more active molecules.
      
All compounds studied are significantly active in the RNA-dependent DNA-polymerase (RDDP) assay, and were not toxic toward the Vero cell line.
      
The resulting data were analyzed and suitable models were developed after identification of the active ranges.
      
Significant (p?=?0.0061) increases of radioactivity were observed in kidney, spleen, and thyroid, which could be exampled by the effects of the extract and/or by the generation of active metabolites.
      
Resulting data were analyzed and suitable models were developed after identification of the active ranges.
      
Under suitable assumptions, the global convergence of this algorithm is proved without assuming the linear independence of the gradient of active constraints.
      
Furthermore, the gradients of active constraints are not requested to be linearly independent.
      
Furthermore, the gradients of active constraints are not requested to be linearly independent.
      
The bioreaction mechanism and kinetic behavior of protein enzymatic hydrolysis for preparing active peptides were investigated to model and characterize the enzymatic hydrolysis curves.
      
 

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