全文获取类型
收费全文 | 454篇 |
免费 | 2篇 |
专业分类
系统科学 | 8篇 |
教育与普及 | 2篇 |
理论与方法论 | 3篇 |
现状及发展 | 39篇 |
研究方法 | 96篇 |
综合类 | 282篇 |
自然研究 | 26篇 |
出版年
2023年 | 1篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 1篇 |
2018年 | 6篇 |
2017年 | 5篇 |
2016年 | 8篇 |
2015年 | 2篇 |
2014年 | 6篇 |
2013年 | 6篇 |
2012年 | 55篇 |
2011年 | 78篇 |
2010年 | 13篇 |
2009年 | 4篇 |
2008年 | 52篇 |
2007年 | 43篇 |
2006年 | 42篇 |
2005年 | 32篇 |
2004年 | 38篇 |
2003年 | 23篇 |
2002年 | 29篇 |
2001年 | 3篇 |
1999年 | 1篇 |
1992年 | 1篇 |
1983年 | 1篇 |
排序方式: 共有456条查询结果,搜索用时 0 毫秒
451.
Khaja R Zhang J MacDonald JR He Y Joseph-George AM Wei J Rafiq MA Qian C Shago M Pantano L Aburatani H Jones K Redon R Hurles M Armengol L Estivill X Mural RJ Lee C Scherer SW Feuk L 《Nature genetics》2006,38(12):1413-1418
Numerous types of DNA variation exist, ranging from SNPs to larger structural alterations such as copy number variants (CNVs) and inversions. Alignment of DNA sequence from different sources has been used to identify SNPs and intermediate-sized variants (ISVs). However, only a small proportion of total heterogeneity is characterized, and little is known of the characteristics of most smaller-sized (<50 kb) variants. Here we show that genome assembly comparison is a robust approach for identification of all classes of genetic variation. Through comparison of two human assemblies (Celera's R27c compilation and the Build 35 reference sequence), we identified megabases of sequence (in the form of 13,534 putative non-SNP events) that were absent, inverted or polymorphic in one assembly. Database comparison and laboratory experimentation further demonstrated overlap or validation for 240 variable regions and confirmed >1.5 million SNPs. Some differences were simple insertions and deletions, but in regions containing CNVs, segmental duplication and repetitive DNA, they were more complex. Our results uncover substantial undescribed variation in humans, highlighting the need for comprehensive annotation strategies to fully interpret genome scanning and personalized sequencing projects. 相似文献
452.
453.
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
454.
Sebaihia M Wren BW Mullany P Fairweather NF Minton N Stabler R Thomson NR Roberts AP Cerdeño-Tárraga AM Wang H Holden MT Wright A Churcher C Quail MA Baker S Bason N Brooks K Chillingworth T Cronin A Davis P Dowd L Fraser A Feltwell T Hance Z Holroyd S Jagels K Moule S Mungall K Price C Rabbinowitsch E Sharp S Simmonds M Stevens K Unwin L Whithead S Dupuy B Dougan G Barrell B Parkhill J 《Nature genetics》2006,38(7):779-786
We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism. 相似文献
455.
DeLuna A Vetsigian K Shoresh N Hegreness M Colón-González M Chao S Kishony R 《Nature genetics》2008,40(5):676-681
Duplicate genes from the whole-genome duplication (WGD) in yeast are often dispensable--removing one copy has little or no phenotypic consequence. It is unknown, however, whether such dispensability reflects insignificance of the ancestral function or compensation from paralogs. Here, using precise competition-based measurements of the fitness cost of single and double deletions, we estimate the exposed fitness contribution of WGD duplicate genes in metabolism and bound the importance of their ancestral pre-duplication function. We find that the functional overlap between paralogs sufficiently explains the apparent dispensability of individual WGD genes. Furthermore, the lower bound on the fitness value of the ancestral function, which is estimated by the degree of synergistic epistasis, is at least as large as the average fitness cost of deleting single non-WGD genes. These results suggest that most metabolic functions encoded by WGD genes are important today and were also important at the time of duplication. 相似文献
456.
Turner DJ Miretti M Rajan D Fiegler H Carter NP Blayney ML Beck S Hurles ME 《Nature genetics》2008,40(1):90-95
Meiotic recombination between highly similar duplicated sequences (nonallelic homologous recombination, NAHR) generates deletions, duplications, inversions and translocations, and it is responsible for genetic diseases known as 'genomic disorders', most of which are caused by altered copy number of dosage-sensitive genes. NAHR hot spots have been identified within some duplicated sequences. We have developed sperm-based assays to measure the de novo rate of reciprocal deletions and duplications at four NAHR hot spots. We used these assays to dissect the relative rates of NAHR between different pairs of duplicated sequences. We show that (i) these NAHR hot spots are specific to meiosis, (ii) deletions are generated at a higher rate than their reciprocal duplications in the male germline and (iii) some of these genomic disorders are likely to have been underascertained clinically, most notably that resulting from the duplication of 7q11, the reciprocal of the deletion causing Williams-Beuren syndrome. 相似文献