全文获取类型
收费全文 | 474篇 |
免费 | 2篇 |
国内免费 | 3篇 |
专业分类
系统科学 | 34篇 |
丛书文集 | 1篇 |
教育与普及 | 1篇 |
理论与方法论 | 3篇 |
现状及发展 | 95篇 |
研究方法 | 97篇 |
综合类 | 234篇 |
自然研究 | 14篇 |
出版年
2021年 | 3篇 |
2020年 | 4篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 3篇 |
2014年 | 5篇 |
2013年 | 8篇 |
2012年 | 27篇 |
2011年 | 66篇 |
2010年 | 10篇 |
2009年 | 2篇 |
2008年 | 39篇 |
2007年 | 38篇 |
2006年 | 36篇 |
2005年 | 32篇 |
2004年 | 27篇 |
2003年 | 19篇 |
2002年 | 30篇 |
2001年 | 8篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1992年 | 6篇 |
1987年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1980年 | 2篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 5篇 |
1971年 | 4篇 |
1970年 | 7篇 |
1969年 | 5篇 |
1968年 | 5篇 |
1967年 | 2篇 |
1966年 | 3篇 |
1965年 | 8篇 |
1963年 | 1篇 |
1962年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有479条查询结果,搜索用时 15 毫秒
391.
392.
393.
Simon S. Gerber Sofia Lejon Michael Locher Johann Schaller 《Cellular and molecular life sciences : CMLS》2010,67(9):1505-1518
The human α2-plasmin inhibitor (A2PI) possesses unique N- and C-terminal extensions that significantly influence its biological activities.
The C-terminal segment, A2PIC (Asn398-Lys452), contains six lysines thought to be involved in the binding to lysine-binding sites in the kringle domains of human plasminogen,
of which four (Lys422, Lys429, Lys436, Lys452) are completely and two (Lys406, Lys415) are partially conserved. Multiple Lys to Ala mutants of A2PIC were expressed in Escherichia coli and used in intrinsic fluorescence titrations with kringle domains K1, K4, K4 + 5, and K1 + 2 + 3 of human plasminogen. We
were able to identify the C-terminal Lys452 as the main binding partner in recombinant A2PIC (rA2PIC) constructs with isolated kringles. We could show a cooperative,
zipper-like enhancement of the interaction between C-terminal Lys452 and internal Lys436 of rA2PIC and isolated K1 + 2 + 3, whereas the other internal lysine residues contribute only to a minor extent to the binding
process. Sulfated Tyr445 in the unique C-terminal segment revealed no influence on the binding affinity to kringle domains. 相似文献
394.
Keshet I Schlesinger Y Farkash S Rand E Hecht M Segal E Pikarski E Young RA Niveleau A Cedar H Simon I 《Nature genetics》2006,38(2):149-153
DNA methylation has a role in the regulation of gene expression during normal mammalian development but can also mediate epigenetic silencing of CpG island genes in cancer and other diseases. Many individual genes (including tumor suppressors) have been shown to undergo de novo methylation in specific tumor types, but the biological logic inherent in this process is not understood. To decipher this mechanism, we have adopted a new approach for detecting CpG island DNA methylation that can be used together with microarray technology. Genome-wide analysis by this technique demonstrated that tumor-specific methylated genes belong to distinct functional categories, have common sequence motifs in their promoters and are found in clusters on chromosomes. In addition, many are already repressed in normal cells. These results are consistent with the hypothesis that cancer-related de novo methylation may come about through an instructive mechanism. 相似文献
395.
396.
Roscioli T Cliffe ST Bloch DB Bell CG Mullan G Taylor PJ Sarris M Wang J Donald JA Kirk EP Ziegler JB Salzer U McDonald GB Wong M Lindeman R Buckley MF 《Nature genetics》2006,38(6):620-622
We describe mutations in the PML nuclear body protein Sp110 in the syndrome veno-occlusive disease with immunodeficiency, an autosomal recessive disorder of severe hypogammaglobulinemia, combined T and B cell immunodeficiency, absent lymph node germinal centers, absent tissue plasma cells and hepatic veno-occlusive disease. This is the first report of the involvement of a nuclear body protein in a human primary immunodeficiency and of high-penetrance genetic mutations in hepatic veno-occlusive disease. 相似文献
397.
Population genomics of human gene expression 总被引:1,自引:0,他引:1
Stranger BE Nica AC Forrest MS Dimas A Bird CP Beazley C Ingle CE Dunning M Flicek P Koller D Montgomery S Tavaré S Deloukas P Dermitzakis ET 《Nature genetics》2007,39(10):1217-1224
Genetic variation influences gene expression, and this variation in gene expression can be efficiently mapped to specific genomic regions and variants. Here we have used gene expression profiling of Epstein-Barr virus-transformed lymphoblastoid cell lines of all 270 individuals genotyped in the HapMap Consortium to elucidate the detailed features of genetic variation underlying gene expression variation. We find that gene expression is heritable and that differentiation between populations is in agreement with earlier small-scale studies. A detailed association analysis of over 2.2 million common SNPs per population (5% frequency in HapMap) with gene expression identified at least 1,348 genes with association signals in cis and at least 180 in trans. Replication in at least one independent population was achieved for 37% of cis signals and 15% of trans signals, respectively. Our results strongly support an abundance of cis-regulatory variation in the human genome. Detection of trans effects is limited but suggests that regulatory variation may be the key primary effect contributing to phenotypic variation in humans. We also explore several methodologies that improve the current state of analysis of gene expression variation. 相似文献
398.
399.
Gudmundsson J Sulem P Manolescu A Amundadottir LT Gudbjartsson D Helgason A Rafnar T Bergthorsson JT Agnarsson BA Baker A Sigurdsson A Benediktsdottir KR Jakobsdottir M Xu J Blondal T Kostic J Sun J Ghosh S Stacey SN Mouy M Saemundsdottir J Backman VM Kristjansson K Tres A Partin AW Albers-Akkers MT Godino-Ivan Marcos J Walsh PC Swinkels DW Navarrete S Isaacs SD Aben KK Graif T Cashy J Ruiz-Echarri M Wiley KE Suarez BK Witjes JA Frigge M Ober C Jonsson E Einarsson GV Mayordomo JI Kiemeney LA 《Nature genetics》2007,39(5):631-637
Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (approximately 42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis. 相似文献
400.