全文获取类型
收费全文 | 72篇 |
免费 | 0篇 |
专业分类
系统科学 | 1篇 |
现状及发展 | 10篇 |
研究方法 | 31篇 |
综合类 | 30篇 |
出版年
2017年 | 1篇 |
2015年 | 1篇 |
2012年 | 5篇 |
2011年 | 9篇 |
2008年 | 13篇 |
2007年 | 9篇 |
2006年 | 2篇 |
2005年 | 1篇 |
2004年 | 5篇 |
2003年 | 2篇 |
2002年 | 4篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1992年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1978年 | 1篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1966年 | 2篇 |
1965年 | 1篇 |
1957年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有72条查询结果,搜索用时 93 毫秒
51.
A framework for variation discovery and genotyping using next-generation DNA sequencing data 总被引:7,自引:0,他引:7
DePristo MA Banks E Poplin R Garimella KV Maguire JR Hartl C Philippakis AA del Angel G Rivas MA Hanna M McKenna A Fennell TJ Kernytsky AM Sivachenko AY Cibulskis K Gabriel SB Altshuler D Daly MJ 《Nature genetics》2011,43(5):491-498
Recent advances in sequencing technology make it possible to comprehensively catalog genetic variation in population samples, creating a foundation for understanding human disease, ancestry and evolution. The amounts of raw data produced are prodigious, and many computational steps are required to translate this output into high-quality variant calls. We present a unified analytic framework to discover and genotype variation among multiple samples simultaneously that achieves sensitive and specific results across five sequencing technologies and three distinct, canonical experimental designs. Our process includes (i) initial read mapping; (ii) local realignment around indels; (iii) base quality score recalibration; (iv) SNP discovery and genotyping to find all potential variants; and (v) machine learning to separate true segregating variation from machine artifacts common to next-generation sequencing technologies. We here discuss the application of these tools, instantiated in the Genome Analysis Toolkit, to deep whole-genome, whole-exome capture and multi-sample low-pass (~4×) 1000 Genomes Project datasets. 相似文献
52.
Ferreira MA O'Donovan MC Meng YA Jones IR Ruderfer DM Jones L Fan J Kirov G Perlis RH Green EK Smoller JW Grozeva D Stone J Nikolov I Chambert K Hamshere ML Nimgaonkar VL Moskvina V Thase ME Caesar S Sachs GS Franklin J Gordon-Smith K Ardlie KG Gabriel SB Fraser C Blumenstiel B Defelice M Breen G Gill M Morris DW Elkin A Muir WJ McGhee KA Williamson R MacIntyre DJ MacLean AW St CD Robinson M Van Beck M Pereira AC Kandaswamy R McQuillin A Collier DA Bass NJ Young AH Lawrence J Ferrier IN 《Nature genetics》2008,40(9):1056-1058
To identify susceptibility loci for bipolar disorder, we tested 1.8 million variants in 4,387 cases and 6,209 controls and identified a region of strong association (rs10994336, P = 9.1 x 10(-9)) in ANK3 (ankyrin G). We also found further support for the previously reported CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel; combined P = 7.0 x 10(-8), rs1006737). Our results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder. 相似文献
53.
Korn JM Kuruvilla FG McCarroll SA Wysoker A Nemesh J Cawley S Hubbell E Veitch J Collins PJ Darvishi K Lee C Nizzari MM Gabriel SB Purcell S Daly MJ Altshuler D 《Nature genetics》2008,40(10):1253-1260
Accurate and complete measurement of single nucleotide (SNP) and copy number (CNV) variants, both common and rare, will be required to understand the role of genetic variation in disease. We present Birdsuite, a four-stage analytical framework instantiated in software for deriving integrated and mutually consistent copy number and SNP genotypes. The method sequentially assigns copy number across regions of common copy number polymorphisms (CNPs), calls genotypes of SNPs, identifies rare CNVs via a hidden Markov model (HMM), and generates an integrated sequence and copy number genotype at every locus (for example, including genotypes such as A-null, AAB and BBB in addition to AA, AB and BB calls). Such genotypes more accurately depict the underlying sequence of each individual, reducing the rate of apparent mendelian inconsistencies. The Birdsuite software is applied here to data from the Affymetrix SNP 6.0 array. Additionally, we describe a method, implemented in PLINK, to utilize these combined SNP and CNV genotypes for association testing with a phenotype. 相似文献
54.
International Consortium for Systemic Lupus Erythematosus Genetics 《Nature genetics》2008,40(2):204-210
Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE. 相似文献
55.
Plenge RM Cotsapas C Davies L Price AL de Bakker PI Maller J Pe'er I Burtt NP Blumenstiel B DeFelice M Parkin M Barry R Winslow W Healy C Graham RR Neale BM Izmailova E Roubenoff R Parker AN Glass R Karlson EW Maher N Hafler DA Lee DM Seldin MF Remmers EF Lee AT Padyukov L Alfredsson L Coblyn J Weinblatt ME Gabriel SB Purcell S Klareskog L Gregersen PK Shadick NA Daly MJ Altshuler D 《Nature genetics》2007,39(12):1477-1482
To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, approximately 150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10(-3), GWA scan; P < 10(-6), replication; P = 10(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 x 10(-6) in WTCCC). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23. 相似文献
56.
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
57.
Martin J Han C Gordon LA Terry A Prabhakar S She X Xie G Hellsten U Chan YM Altherr M Couronne O Aerts A Bajorek E Black S Blumer H Branscomb E Brown NC Bruno WJ Buckingham JM Callen DF Campbell CS Campbell ML Campbell EW Caoile C Challacombe JF Chasteen LA Chertkov O Chi HC Christensen M Clark LM Cohn JD Denys M Detter JC Dickson M Dimitrijevic-Bussod M Escobar J Fawcett JJ Flowers D Fotopulos D Glavina T Gomez M Gonzales E Goodstein D Goodwin LA Grady DL Grigoriev I Groza M Hammon N Hawkins T 《Nature》2004,432(7020):988-994
58.
Grimwood J Gordon LA Olsen A Terry A Schmutz J Lamerdin J Hellsten U Goodstein D Couronne O Tran-Gyamfi M Aerts A Altherr M Ashworth L Bajorek E Black S Branscomb E Caenepeel S Carrano A Caoile C Chan YM Christensen M Cleland CA Copeland A Dalin E Dehal P Denys M Detter JC Escobar J Flowers D Fotopulos D Garcia C Georgescu AM Glavina T Gomez M Gonzales E Groza M Hammon N Hawkins T Haydu L Ho I Huang W Israni S Jett J Kadner K Kimball H Kobayashi A Larionov V Leem SH Lopez F Lou Y Lowry S 《Nature》2004,428(6982):529-535
Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G + C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu. 相似文献
59.
60.