全文获取类型
收费全文 | 332篇 |
免费 | 4篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 2篇 |
教育与普及 | 3篇 |
理论与方法论 | 3篇 |
现状及发展 | 51篇 |
研究方法 | 37篇 |
综合类 | 237篇 |
自然研究 | 4篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2018年 | 5篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 3篇 |
2014年 | 3篇 |
2013年 | 2篇 |
2012年 | 19篇 |
2011年 | 37篇 |
2010年 | 13篇 |
2009年 | 1篇 |
2008年 | 13篇 |
2007年 | 21篇 |
2006年 | 20篇 |
2005年 | 17篇 |
2004年 | 9篇 |
2003年 | 21篇 |
2002年 | 57篇 |
2001年 | 40篇 |
2000年 | 7篇 |
1997年 | 2篇 |
1993年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1980年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 3篇 |
1971年 | 1篇 |
1969年 | 2篇 |
1966年 | 2篇 |
1965年 | 2篇 |
1964年 | 4篇 |
1961年 | 2篇 |
排序方式: 共有337条查询结果,搜索用时 0 毫秒
331.
332.
333.
334.
Zhou Z Feng H Zhou BR Ghirlando R Hu K Zwolak A Miller Jenkins LM Xiao H Tjandra N Wu C Bai Y 《Nature》2011,472(7342):234-237
The centromere is a unique chromosomal locus that ensures accurate segregation of chromosomes during cell division by directing the assembly of a multiprotein complex, the kinetochore. The centromere is marked by a conserved variant of conventional histone H3 termed CenH3 or CENP-A (ref. 2). A conserved motif of CenH3, the CATD, defined by loop 1 and helix 2 of the histone fold, is necessary and sufficient for specifying centromere functions of CenH3 (refs 3, 4). The structural basis of this specification is of particular interest. Yeast Scm3 and human HJURP are conserved non-histone proteins that interact physically with the (CenH3-H4)(2) heterotetramer and are required for the deposition of CenH3 at centromeres in vivo. Here we have elucidated the structural basis for recognition of budding yeast (Saccharomyces cerevisiae) CenH3 (called Cse4) by Scm3. We solved the structure of the Cse4-binding domain (CBD) of Scm3 in complex with Cse4 and H4 in a single chain model. An α-helix and an irregular loop at the conserved amino terminus and a shorter α-helix at the carboxy terminus of Scm3(CBD) wraps around the Cse4-H4 dimer. Four Cse4-specific residues in the N-terminal region of helix 2 are sufficient for specific recognition by conserved and functionally important residues in the N-terminal helix of Scm3 through formation of a hydrophobic cluster. Scm3(CBD) induces major conformational changes and sterically occludes DNA-binding sites in the structure of Cse4 and H4. These findings have implications for the assembly and architecture of the centromeric nucleosome. 相似文献
335.
Bejerano G Lowe CB Ahituv N King B Siepel A Salama SR Rubin EM Kent WJ Haussler D 《Nature》2006,441(7089):87-90
Hundreds of highly conserved distal cis-regulatory elements have been characterized so far in vertebrate genomes. Many thousands more are predicted on the basis of comparative genomics. However, in stark contrast to the genes that they regulate, in invertebrates virtually none of these regions can be traced by using sequence similarity, leaving their evolutionary origins obscure. Here we show that a class of conserved, primarily non-coding regions in tetrapods originated from a previously unknown short interspersed repetitive element (SINE) retroposon family that was active in the Sarcopterygii (lobe-finned fishes and terrestrial vertebrates) in the Silurian period at least 410 million years ago (ref. 4), and seems to be recently active in the 'living fossil' Indonesian coelacanth, Latimeria menadoensis. Using a mouse enhancer assay we show that one copy, 0.5 million bases from the neuro-developmental gene ISL1, is an enhancer that recapitulates multiple aspects of Isl1 expression patterns. Several other copies represent new, possibly regulatory, alternatively spliced exons in the middle of pre-existing Sarcopterygian genes. One of these, a more than 200-base-pair ultraconserved region, 100% identical in mammals, and 80% identical to the coelacanth SINE, contains a 31-amino-acid-residue alternatively spliced exon of the messenger RNA processing gene PCBP2 (ref. 6). These add to a growing list of examples in which relics of transposable elements have acquired a function that serves their host, a process termed 'exaptation', and provide an origin for at least some of the many highly conserved vertebrate-specific genomic sequences. 相似文献
336.
Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR 总被引:1,自引:0,他引:1
Lange A Giller K Hornig S Martin-Eauclaire MF Pongs O Becker S Baldus M 《Nature》2006,440(7086):959-962
The active site of potassium (K+) channels catalyses the transport of K+ ions across the plasma membrane--similar to the catalytic function of the active site of an enzyme--and is inhibited by toxins from scorpion venom. On the basis of the conserved structures of K+ pore regions and scorpion toxins, detailed structures for the K+ channel-scorpion toxin binding interface have been proposed. In these models and in previous solution-state nuclear magnetic resonance (NMR) studies using detergent-solubilized membrane proteins, scorpion toxins were docked to the extracellular entrance of the K+ channel pore assuming rigid, preformed binding sites. Using high-resolution solid-state NMR spectroscopy, here we show that high-affinity binding of the scorpion toxin kaliotoxin to a chimaeric K+ channel (KcsA-Kv1.3) is associated with significant structural rearrangements in both molecules. Our approach involves a combined analysis of chemical shifts and proton-proton distances and demonstrates that solid-state NMR is a sensitive method for analysing the structure of a membrane protein-inhibitor complex. We propose that structural flexibility of the K+ channel and the toxin represents an important determinant for the high specificity of toxin-K+ channel interactions. 相似文献
337.
Computational modelling has suggested that at least two counteracting forces are required for establishing topographic maps. Ephrin-family proteins are required for both anterior-posterior and medial-lateral topographic mapping, but the opposing forces have not been well characterized. Wnt-family proteins are recently discovered axon guidance cues. We find that Wnt3 is expressed in a medial-lateral decreasing gradient in chick optic tectum and mouse superior colliculus. Retinal ganglion cell (RGC) axons from different dorsal-ventral positions showed graded and biphasic response to Wnt3 in a concentration-dependent manner. Wnt3 repulsion is mediated by Ryk, expressed in a ventral-to-dorsal decreasing gradient, whereas attraction of dorsal axons at lower Wnt3 concentrations is mediated by Frizzled(s). Overexpression of Wnt3 in the lateral tectum repelled the termination zones of dorsal RGC axons in vivo. Expression of a dominant-negative Ryk in dorsal RGC axons caused a medial shift of the termination zones, promoting medially directed interstitial branches and eliminating laterally directed branches. Therefore, a classical morphogen, Wnt3, acting as an axon guidance molecule, plays a role in retinotectal mapping along the medial-lateral axis, counterbalancing the medial-directed EphrinB1-EphB activity. 相似文献