全文获取类型
收费全文 | 5745篇 |
免费 | 450篇 |
国内免费 | 328篇 |
专业分类
6523篇 |
出版年
2024年 | 22篇 |
2023年 | 154篇 |
2022年 | 226篇 |
2021年 | 272篇 |
2020年 | 287篇 |
2019年 | 365篇 |
2018年 | 315篇 |
2017年 | 237篇 |
2016年 | 282篇 |
2015年 | 288篇 |
2014年 | 405篇 |
2013年 | 615篇 |
2012年 | 234篇 |
2011年 | 276篇 |
2010年 | 200篇 |
2009年 | 251篇 |
2008年 | 275篇 |
2007年 | 248篇 |
2006年 | 239篇 |
2005年 | 196篇 |
2004年 | 172篇 |
2003年 | 136篇 |
2002年 | 155篇 |
2001年 | 91篇 |
2000年 | 55篇 |
1999年 | 67篇 |
1998年 | 73篇 |
1997年 | 52篇 |
1996年 | 43篇 |
1995年 | 37篇 |
1994年 | 37篇 |
1993年 | 31篇 |
1992年 | 16篇 |
1991年 | 21篇 |
1990年 | 16篇 |
1989年 | 18篇 |
1988年 | 8篇 |
1987年 | 12篇 |
1986年 | 14篇 |
1985年 | 12篇 |
1984年 | 23篇 |
1983年 | 11篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1973年 | 2篇 |
排序方式: 共有6523条查询结果,搜索用时 0 毫秒
991.
992.
993.
994.
995.
996.
Prabu Manoharan 《Journal of biomolecular structure & dynamics》2018,36(7):1878-1892
Traditional structure-based virtual screening method to identify drug-like small molecules for BACE1 is so far unsuccessful. Location of BACE1, poor Blood Brain Barrier permeability and P-glycoprotein (Pgp) susceptibility of the inhibitors make it even more difficult. Fragment-based drug design method is suitable for efficient optimization of initial hit molecules for target like BACE1. We have developed a fragment-based virtual screening approach to identify/optimize the fragment molecules as a starting point. This method combines the shape, electrostatic, and pharmacophoric features of known fragment molecules, bound to protein conjugate crystal structure, and aims to identify both chemically and energetically feasible small fragment ligands that bind to BACE1 active site. The two top-ranked fragment hits were subjected for a 53 ns MD simulation. Principle component analysis and free energy landscape analysis reveal that the new ligands show the characteristic features of established BACE1 inhibitors. The potent method employed in this study may serve for the development of potential lead molecules for BACE1-directed Alzheimer’s disease therapeutics. 相似文献
997.
998.
999.
Brenda K Eustace Andrea Buchstaller Daniel G Jay 《Briefings in Functional Genomics and Prot》2002,1(3):257-265
Recent advances in genomics and proteomics have generated a change in emphasis from hypothesis-based to discovery-based investigations. Genomic and proteomic studies based on differential expression microarrays or comparative proteomics often provide many potential candidates for functionally important roles in normal and diseased cells. High throughput technologies to address protein and gene function in situ are still necessary to exploit these emerging advances in gene and protein discovery in order to validate these identified targets. The pharmaceutical industry is particularly interested in target validation, and has identified it as the critical early step in drug discovery. An especially powerful approach to target validation is a direct protein knockdown strategy called chromophore-assisted laser inactivation (CALI) which is a means of testing the role of specific proteins in particular cellular processes. Recent developments in CALI allow for its high throughput application to address many proteins in tandem. Thus, CALI may have applications for high throughput hypothesis testing, target validation or proteome-wide screening. 相似文献
1000.