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排序方式: 共有74条查询结果,搜索用时 31 毫秒
51.
Evans DM Spencer CC Pointon JJ Su Z Harvey D Kochan G Oppermann U Opperman U Dilthey A Pirinen M Stone MA Appleton L Moutsianas L Moutsianis L Leslie S Wordsworth T Kenna TJ Karaderi T Thomas GP Ward MM Weisman MH Farrar C Bradbury LA Danoy P Inman RD Maksymowych W Gladman D Rahman P;Spondyloarthritis Research Consortium of Canada 《Nature genetics》2011,43(8):761-767
Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides. 相似文献
52.
Goudie DR D'Alessandro M Merriman B Lee H Szeverényi I Avery S O'Connor BD Nelson SF Coats SE Stewart A Christie L Pichert G Friedel J Hayes I Burrows N Whittaker S Gerdes AM Broesby-Olsen S Ferguson-Smith MA Verma C Lunny DP Reversade B Lane EB 《Nature genetics》2011,43(4):365-369
Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars. High-throughput genomic sequencing of a conservative estimate (24.2 Mb) of the disease locus on chromosome 9 using exon array capture identified independent mutations in TGFBR1 in three unrelated families. Subsequent dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families, firmly establishing TGFBR1 as the causative gene. The nature of the sequence variants, which include mutations in the extracellular ligand-binding domain and a series of truncating mutations in the kinase domain, indicates a clear genotype-phenotype correlation between loss-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer. 相似文献
53.
Haiman CA Patterson N Freedman ML Myers SR Pike MC Waliszewska A Neubauer J Tandon A Schirmer C McDonald GJ Greenway SC Stram DO Le Marchand L Kolonel LN Frasco M Wong D Pooler LC Ardlie K Oakley-Girvan I Whittemore AS Cooney KA John EM Ingles SA Altshuler D Henderson BE Reich D 《Nature genetics》2007,39(5):638-644
After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein. 相似文献
54.
55.
INTERMEDIUM-C, a modifier of lateral spikelet fertility in barley, is an ortholog of the maize domestication gene TEOSINTE BRANCHED 1 总被引:1,自引:0,他引:1
Ramsay L Comadran J Druka A Marshall DF Thomas WT Macaulay M MacKenzie K Simpson C Fuller J Bonar N Hayes PM Lundqvist U Franckowiak JD Close TJ Muehlbauer GJ Waugh R 《Nature genetics》2011,43(2):169-172
The domestication of cereals has involved common changes in morphological features, such as seed size, seed retention and modification of vegetative and inflorescence architecture that ultimately contributed to an increase in harvested yield. In barley, this process has resulted in two different cultivated types, two-rowed and six-rowed forms, both derived from the wild two-rowed ancestor, with archaeo-botanical evidence indicating the origin of six-rowed barley early in the domestication of the species, some 8,600-8,000 years ago. Variation at SIX-ROWED SPIKE 1 (VRS1) is sufficient to control this phenotype. However, phenotypes imposed by VRS1 alleles are modified by alleles at the INTERMEDIUM-C (INT-C) locus. Here we show that INT-C is an ortholog of the maize domestication gene TEOSINTE BRANCHED 1 (TB1) and identify 17 coding mutations in barley TB1 correlated with lateral spikelet fertility phenotypes. 相似文献
56.
Dunlop MG Dobbins SE Farrington SM Jones AM Palles C Whiffin N Tenesa A Spain S Broderick P Ooi LY Domingo E Smillie C Henrion M Frampton M Martin L Grimes G Gorman M Semple C Ma YP Barclay E Prendergast J Cazier JB Olver B Penegar S Lubbe S Chander I Carvajal-Carmona LG Ballereau S Lloyd A Vijayakrishnan J Zgaga L Rudan I Theodoratou E;Colorectal Tumour Gene Identification 《Nature genetics》2012,44(7):770-776
We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC. 相似文献
57.
Enciso-Mora V Broderick P Ma Y Jarrett RF Hjalgrim H Hemminki K van den Berg A Olver B Lloyd A Dobbins SE Lightfoot T van Leeuwen FE Försti A Diepstra A Broeks A Vijayakrishnan J Shield L Lake A Montgomery D Roman E Engert A von Strandmann EP Reiners KS Nolte IM Smedby KE Adami HO Russell NS Glimelius B Hamilton-Dutoit S de Bruin M Ryder LP Molin D Sorensen KM Chang ET Taylor M Cooke R Hofstra R Westers H van Wezel T van Eijk R Ashworth A Rostgaard K Melbye M Swerdlow AJ Houlston RS 《Nature genetics》2010,42(12):1126-1130
To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10(-8)), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10(-13)) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10(-8)). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10(-50)). These data provide new insight into the pathogenesis of cHL. 相似文献
58.
Cox A Dunning AM Garcia-Closas M Balasubramanian S Reed MW Pooley KA Scollen S Baynes C Ponder BA Chanock S Lissowska J Brinton L Peplonska B Southey MC Hopper JL McCredie MR Giles GG Fletcher O Johnson N dos Santos Silva I Gibson L Bojesen SE Nordestgaard BG Axelsson CK Torres D Hamann U Justenhoven C Brauch H Chang-Claude J Kropp S Risch A Wang-Gohrke S Schürmann P Bogdanova N Dörk T Fagerholm R Aaltonen K Blomqvist C Nevanlinna H Seal S Renwick A Stratton MR Rahman N Sangrajrang S Hughes D 《Nature genetics》2007,39(3):352-358
The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies. 相似文献
59.
60.
Volatile content of lunar volcanic glasses and the presence of water in the Moon's interior 总被引:1,自引:0,他引:1
The Moon is generally thought to have formed and evolved through a single or a series of catastrophic heating events, during which most of the highly volatile elements were lost. Hydrogen, being the lightest element, is believed to have been completely lost during this period. Here we make use of considerable advances in secondary ion mass spectrometry to obtain improved limits on the indigenous volatile (CO(2), H(2)O, F, S and Cl) contents of the most primitive basalts in the Moon-the lunar volcanic glasses. Although the pre-eruptive water content of the lunar volcanic glasses cannot be precisely constrained, numerical modelling of diffusive degassing of the very-low-Ti glasses provides a best estimate of 745 p.p.m. water, with a minimum of 260 p.p.m. at the 95 per cent confidence level. Our results indicate that, contrary to prevailing ideas, the bulk Moon might not be entirely depleted in highly volatile elements, including water. Thus, the presence of water must be considered in models constraining the Moon's formation and its thermal and chemical evolution. 相似文献