全文获取类型
收费全文 | 389篇 |
免费 | 11篇 |
国内免费 | 2篇 |
专业分类
系统科学 | 7篇 |
丛书文集 | 1篇 |
教育与普及 | 2篇 |
理论与方法论 | 4篇 |
现状及发展 | 79篇 |
研究方法 | 90篇 |
综合类 | 214篇 |
自然研究 | 5篇 |
出版年
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 10篇 |
2017年 | 8篇 |
2016年 | 7篇 |
2015年 | 4篇 |
2014年 | 11篇 |
2013年 | 5篇 |
2012年 | 50篇 |
2011年 | 54篇 |
2010年 | 23篇 |
2009年 | 6篇 |
2008年 | 35篇 |
2007年 | 32篇 |
2006年 | 34篇 |
2005年 | 26篇 |
2004年 | 26篇 |
2003年 | 17篇 |
2002年 | 26篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1975年 | 3篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1957年 | 1篇 |
1956年 | 1篇 |
1948年 | 1篇 |
排序方式: 共有402条查询结果,搜索用时 46 毫秒
401.
Holliday proposed a four-way DNA junction as an intermediate in homologous recombination, and such Holliday junctions have since been identified as a central component in DNA recombination and repair. Phage T4 endonuclease VII (endo VII) was the first enzyme shown to resolve Holliday junctions into duplex DNAs by introducing symmetrical nicks in equivalent strands. Several Holliday junction resolvases have since been characterized, but an atomic structure of a resolvase complex with a Holliday junction remained elusive. Here we report the crystal structure of an inactive T4 endo VII(N62D) complexed with an immobile four-way junction with alternating arm lengths of 10 and 14 base pairs. The junction is a hybrid of the conventional square-planar and stacked-X conformation. Endo VII protrudes into the junction point from the minor groove side, opening it to a 14 A x 32 A parallelogram. This interaction interrupts the coaxial stacking, yet every base pair surrounding the junction remains intact. Additional interactions involve the positively charged protein and DNA phosphate backbones. Each scissile phosphate that is two base pairs from the crossover interacts with a Mg2+ ion in the active site. The similar overall shape and surface charge potential of the Holliday junction resolvases endo VII, RuvC, Ydc2, Hjc and RecU, despite having different folds, active site composition and DNA sequence preference, suggest a conserved binding mode for Holliday junctions. 相似文献
402.
Sladek R Rocheleau G Rung J Dina C Shen L Serre D Boutin P Vincent D Belisle A Hadjadj S Balkau B Heude B Charpentier G Hudson TJ Montpetit A Pshezhetsky AV Prentki M Posner BI Balding DJ Meyre D Polychronakos C Froguel P 《Nature》2007,445(7130):881-885
Type 2 diabetes mellitus results from the interaction of environmental factors with a combination of genetic variants, most of which were hitherto unknown. A systematic search for these variants was recently made possible by the development of high-density arrays that permit the genotyping of hundreds of thousands of polymorphisms. We tested 392,935 single-nucleotide polymorphisms in a French case-control cohort. Markers with the most significant difference in genotype frequencies between cases of type 2 diabetes and controls were fast-tracked for testing in a second cohort. This identified four loci containing variants that confer type 2 diabetes risk, in addition to confirming the known association with the TCF7L2 gene. These loci include a non-synonymous polymorphism in the zinc transporter SLC30A8, which is expressed exclusively in insulin-producing beta-cells, and two linkage disequilibrium blocks that contain genes potentially involved in beta-cell development or function (IDE-KIF11-HHEX and EXT2-ALX4). These associations explain a substantial portion of disease risk and constitute proof of principle for the genome-wide approach to the elucidation of complex genetic traits. 相似文献