全文获取类型
收费全文 | 195篇 |
免费 | 0篇 |
国内免费 | 3篇 |
专业分类
系统科学 | 3篇 |
教育与普及 | 1篇 |
理论与方法论 | 2篇 |
现状及发展 | 49篇 |
研究方法 | 15篇 |
综合类 | 124篇 |
自然研究 | 4篇 |
出版年
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 1篇 |
2014年 | 2篇 |
2013年 | 1篇 |
2012年 | 9篇 |
2011年 | 15篇 |
2010年 | 4篇 |
2009年 | 1篇 |
2008年 | 9篇 |
2007年 | 5篇 |
2006年 | 13篇 |
2005年 | 8篇 |
2004年 | 10篇 |
2003年 | 6篇 |
2002年 | 7篇 |
2001年 | 8篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 6篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1971年 | 7篇 |
1970年 | 8篇 |
1969年 | 5篇 |
1968年 | 3篇 |
1967年 | 3篇 |
1966年 | 7篇 |
1965年 | 3篇 |
1963年 | 1篇 |
1958年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有198条查询结果,搜索用时 0 毫秒
151.
Ribozymes use specific RNA-RNA interactions for substrate binding and active-site formation. Self-splicing group I introns have approximately 70 nucleotides constituting the core, a region containing sequences and structures indispensable for catalytic function. The catalytic core must interact with the substrates used for the two steps of the self-splicing reaction, that is, guanosine, the 5'-splice-site helix (P1) and the 3' splice site. Mutational evidence suggests that core sequences near segment J6/7 that joins the base-paired stems P6 and P7, and the bulged base of P7(5'), participate in binding guanosine substrate, but nothing is known about the interactions between the core, the 5'-splice-site helix and the 3' splice site. On the basis of comparative sequence data, it has been suggested that two specific bases in the catalytic core of group I introns might form a binding sequence for the 3' splice site. Here we present genetic evidence that such a binding site exists in the core of the Tetrahymena large subunit ribosomal RNA intron. We demonstrate that this pairing, termed P9.0, is functionally important in the exon ligation step of self-splicing, but is not itself responsible for 3'-splice-site selection. 相似文献
152.
Genes mirror geography within Europe 总被引:1,自引:0,他引:1
Novembre J Johnson T Bryc K Kutalik Z Boyko AR Auton A Indap A King KS Bergmann S Nelson MR Stephens M Bustamante CD 《Nature》2008,456(7218):98-101
Understanding the genetic structure of human populations is of fundamental interest to medical, forensic and anthropological sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation and suggest the potential to use large samples to uncover variation among closely spaced populations. Here we characterize genetic variation in a sample of 3,000 European individuals genotyped at over half a million variable DNA sites in the human genome. Despite low average levels of genetic differentiation among Europeans, we find a close correspondence between genetic and geographic distances; indeed, a geographical map of Europe arises naturally as an efficient two-dimensional summary of genetic variation in Europeans. The results emphasize that when mapping the genetic basis of a disease phenotype, spurious associations can arise if genetic structure is not properly accounted for. In addition, the results are relevant to the prospects of genetic ancestry testing; an individual's DNA can be used to infer their geographic origin with surprising accuracy-often to within a few hundred kilometres. 相似文献
153.
154.
Meimaridou E Kowalczyk J Guasti L Hughes CR Wagner F Frommolt P Nürnberg P Mann NP Banerjee R Saka HN Chapple JP King PJ Clark AJ Metherell LA 《Nature genetics》2012,44(7):740-742
Using targeted exome sequencing, we identified mutations in NNT, an antioxidant defense gene, in individuals with familial glucocorticoid deficiency. In mice with Nnt loss, higher levels of adrenocortical cell apoptosis and impaired glucocorticoid production were observed. NNT knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased reactive oxygen species (ROS) levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands. 相似文献
155.
Zhiliang Chen Xuanyang Zhang Feng Shen Jixiang Zhao Yuping Liu Wenqing Tang Clark B. Burchfiel Robert W. King Leigh H. Royden 《科学通报(英文版)》1999,44(19):1804-1804
Through GPS carrier phases observation in southwestern China during 1991–1997, the velocity field within eastern Qinghai-Xizang
(Tibet) and its neighbour regions has been established. The velocity of those sites in and west of Chuan-Dian block is mostly
5–10 mm · a™1 relative to the fiduciary station CHDU (Chengdu), and the motion in Chuan-Qing and Yangtze blocks east of the Xianshuihe-Xiaojiang
fault is weak with a velocity of about 0–7 mm · a−1. The velocity vector in these areas indicates a clockwise rotation vortex rather than the so-called intensive eastward pushing
or eastward escape. The main pattern of the crustal deformation is a clockwise rotation vortex structure and a differential
slip along the boundary fault between different blocks. 相似文献
156.
157.
Climate policy: Oil's tipping point has passed 总被引:1,自引:0,他引:1
158.
Garnett MJ Edelman EJ Heidorn SJ Greenman CD Dastur A Lau KW Greninger P Thompson IR Luo X Soares J Liu Q Iorio F Surdez D Chen L Milano RJ Bignell GR Tam AT Davies H Stevenson JA Barthorpe S Lutz SR Kogera F Lawrence K McLaren-Douglas A Mitropoulos X Mironenko T Thi H Richardson L Zhou W Jewitt F Zhang T O'Brien P Boisvert JL Price S Hur W Yang W Deng X Butler A Choi HG Chang JW Baselga J Stamenkovic I Engelman JA Sharma SV Delattre O Saez-Rodriguez J Gray NS Settleman J Futreal PA Haber DA 《Nature》2012,483(7391):570-575
Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies. 相似文献
159.
160.
Preweaning malnutrition permanently reduced brain size and cellular content but in spite of changes in the adrenocotical stress response no learning deficit was observed. Differential rearing environments did not influence the effects of malnutrition. 相似文献