全文获取类型
收费全文 | 258篇 |
免费 | 11篇 |
出版年
2021年 | 3篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 9篇 |
2014年 | 9篇 |
2013年 | 11篇 |
2012年 | 17篇 |
2011年 | 17篇 |
2010年 | 23篇 |
2009年 | 18篇 |
2008年 | 15篇 |
2007年 | 15篇 |
2006年 | 14篇 |
2005年 | 9篇 |
2004年 | 7篇 |
2003年 | 5篇 |
2002年 | 5篇 |
2001年 | 5篇 |
2000年 | 6篇 |
1999年 | 7篇 |
1998年 | 7篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1990年 | 2篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 2篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1962年 | 1篇 |
1955年 | 1篇 |
1952年 | 1篇 |
1948年 | 1篇 |
1947年 | 1篇 |
排序方式: 共有269条查询结果,搜索用时 375 毫秒
31.
32.
Background
Expression systems based on self-cleavable intein domains allow the generation of recombinant proteins with a C-terminal thioester. This uniquely reactive C-terminus can be used in native chemical ligation reactions to introduce synthetic groups or to immobilize proteins on surfaces and nanoparticles. Unfortunately, common refolding procedures for recombinant proteins that contain disulfide bonds do not preserve the thioester functionality and therefore novel refolding procedures need to be developed. 相似文献33.
McBriar MD Clader JW Chu I Del Vecchio RA Favreau L Greenlee WJ Hyde LA Nomeir AA Parker EM Pissarnitski DA Song L Zhang L Zhao Z 《Bioorganic & medicinal chemistry letters》2008,18(1):215-219
The design of amide and heteroaryl amide isosteres as replacements for the carbamate substructure in previously disclosed 2,6-disubstituted piperidine N-arylsulfonamides is described. In several cases, amides lessened CYP liabilities in this class of gamma-secretase inhibitors. Selected compounds showed significant reduction of Abeta levels upon oral dosing in a transgenic murine model of Alzheimer's disease. 相似文献
34.
Ginny D. Ho John Anthes Ana Bercovici John P. Caldwell Kuo-Chi Cheng Xiaoming Cui Ahmad Fawzi Xiomara Fernandez William J. Greenlee John Hey Walter Korfmacher Sherry X. Lu Robbie L. McLeod Fay Ng April Smith Torhan Zheng Tan Deen Tulshian Geoffrey B. Varty Xiaoying Xu Hongtao Zhang 《Bioorganic & medicinal chemistry letters》2009,19(9):2519-2523
The discovery of 1 as a high-affinity ligand for the nociceptin receptor has led to the synthesis of a series of tropane (8-methyl-8-azabicyclo[3.2.1]octane) derivatives as optimized ligands. These compounds exhibit high affinity for the nociceptin receptor, moderate to excellent selectivity over the opioid μ receptor, and behave as full agonists. In this Letter, we present the synthesis and highlight the structure–activity relationship of tropane derivatives culminating in the identification of 24 and 32 as potent and orally active antitussive and anxiolytic agents. The in vitro and in vivo activities, pharmacokinetic profile, and the hPXR activity, which predicts the potential 3A4 induction in human, are disclosed. 相似文献
35.
Zhaoning Zhu Zhong-Yue Sun Yuanzan Ye Brian McKittrick William Greenlee Michael Czarniecki Ahmad Fawzi Hongtao Zhang Jean E. Lachowicz 《Bioorganic & medicinal chemistry letters》2009,19(17):5218-5221
A series of novel 1,3-benzodiazapine based D1 antagonists was designed according to the understanding of pharmacophore models derived from SCH 23390 (1b), a potent and selective D1 antagonist. The new design features an achiral cyclic-amidine that maintains desired basicity. Solid phase synthesis was developed for SAR development of the novel dopamine antagonists. 相似文献
36.
37.
38.
Jorn R De Haan Ester Piek Rene C van Schaik Jacob de Vlieg Susanne Bauerschmidt Lutgarde MC Buydens Ron Wehrens 《BMC bioinformatics》2010,11(1):158
Background
Gene expression data can be analyzed by summarizing groups of individual gene expression profiles based on GO annotation information. The mean expression profile per group can then be used to identify interesting GO categories in relation to the experimental settings. However, the expression profiles present in GO classes are often heterogeneous, i.e., there are several different expression profiles within one class. As a result, important experimental findings can be obscured because the summarizing profile does not seem to be of interest. We propose to tackle this problem by finding homogeneous subclasses within GO categories: preclustering. 相似文献39.
Wu WL Burnett DA Caplen MA Domalski MS Bennett C Greenlee WJ Hawes BE O'Neill K Weig B Weston D Spar B Kowalski T 《Bioorganic & medicinal chemistry letters》2006,16(14):3674-3678
Biaryl urea lead compound 1 was discovered earlier in our MCH antagonist program. Novel benzimidazole analogues with increased chemical stability, devoid of the potential carcinogenic liability associated with a biarylamine moiety, were synthesized and evaluated to be potent MCH R1 antagonists. Two compounds in this series have demonstrated in vivo efficacy in a rodent obesity model. 相似文献
40.