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排序方式: 共有174条查询结果,搜索用时 421 毫秒
41.
Allen M Heinzmann A Noguchi E Abecasis G Broxholme J Ponting CP Bhattacharyya S Tinsley J Zhang Y Holt R Jones EY Lench N Carey A Jones H Dickens NJ Dimon C Nicholls R Baker C Xue L Townsend E Kabesch M Weiland SK Carr D von Mutius E Adcock IM Barnes PJ Lathrop GM Edwards M Moffatt MF Cookson WO 《Nature genetics》2003,35(3):258-263
Asthma is a common disease in children and young adults. Four separate reports have linked asthma and related phenotypes to an ill-defined interval between 2q14 and 2q32 (refs. 1-4), and two mouse genome screens have linked bronchial hyper-responsiveness to the region homologous to 2q14 (refs. 5,6). We found and replicated association between asthma and the D2S308 microsatellite, 800 kb distal to the IL1 cluster on 2q14. We sequenced the surrounding region and constructed a comprehensive, high-density, single-nucleotide polymorphism (SNP) linkage disequilibrium (LD) map. SNP association was limited to the initial exons of a solitary gene of 3.6 kb (DPP10), which extends over 1 Mb of genomic DNA. DPP10 encodes a homolog of dipeptidyl peptidases (DPPs) that cleave terminal dipeptides from cytokines and chemokines, and it presents a potential new target for asthma therapy. 相似文献
42.
43.
Characterization of murine non-adherent bone marrow cells leading to recovery of endogenous hematopoiesis 总被引:1,自引:1,他引:0
Stephan Fricke Christian Fricke Christopher Oelkrug Nadja Hilger Uta Sch?nfelder Manja Kamprad J?rg Lehmann Johannes Boltze Frank Emmrich Ulrich Sack 《Cellular and molecular life sciences : CMLS》2010,67(23):4095-4106
Non-adherent bone marrow-derived cells (NA-BMCs) are a mixed cell population that can give rise to multiple mesenchymal phenotypes
and that facilitates hematopoietic recovery. We characterized NA-BMCs by flow cytometry, fibroblast colony-forming units (CFU-f),
real-time PCR, and in in vivo experiments. In comparison to adherent cells, NA-BMCs expressed high levels of CD11b+ and CD90+ within the CD45+ cell fraction. CFU-f were significantly declining over the cultivation period, but NA-BMCs were still able to form CFU-f
after 5 days. Gene expression analysis of allogeneic NA-BMCs compared to bone marrow (BM) indicates that NA-BMCs contain stromal,
mesenchymal, endothelial cells and monocytes, but less osteoid, lymphoid, and erythroid cells, and hematopoietic stem cells.
Histopathological data and analysis of weight showed an excellent recovery and organ repair of lethally irradiated mice after
NA-BMC transplantation with a normal composition of the BM. 相似文献
44.
Ellinghaus E Ellinghaus D Stuart PE Nair RP Debrus S Raelson JV Belouchi M Fournier H Reinhard C Ding J Li Y Tejasvi T Gudjonsson J Stoll SW Voorhees JJ Lambert S Weidinger S Eberlein B Kunz M Rahman P Gladman DD Gieger C Wichmann HE Karlsen TH Mayr G Albrecht M Kabelitz D Mrowietz U Abecasis GR Elder JT Schreiber S Weichenthal M Franke A 《Nature genetics》2010,42(11):991-995
45.
de Bakker PI McVean G Sabeti PC Miretti MM Green T Marchini J Ke X Monsuur AJ Whittaker P Delgado M Morrison J Richardson A Walsh EC Gao X Galver L Hart J Hafler DA Pericak-Vance M Todd JA Daly MJ Trowsdale J Wijmenga C Vyse TJ Beck S Murray SS Carrington M Gregory S Deloukas P Rioux JD 《Nature genetics》2006,38(10):1166-1172
The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes. 相似文献
46.
Rivas MA Beaudoin M Gardet A Stevens C Sharma Y Zhang CK Boucher G Ripke S Ellinghaus D Burtt N Fennell T Kirby A Latiano A Goyette P Green T Halfvarson J Haritunians T Korn JM Kuruvilla F Lagacé C Neale B Lo KS Schumm P Törkvist L;National Institute of Diabetes Digestive Kidney Diseases Inflammatory Bowel Disease Genetics Consortium 《Nature genetics》2011,43(11):1066-1073
More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 × 10(-16), odds ratio ≈ 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models. 相似文献
47.
Cao J Schneeberger K Ossowski S Günther T Bender S Fitz J Koenig D Lanz C Stegle O Lippert C Wang X Ott F Müller J Alonso-Blanco C Borgwardt K Schmid KJ Weigel D 《Nature genetics》2011,43(10):956-963
The plant Arabidopsis thaliana occurs naturally in many different habitats throughout Eurasia. As a foundation for identifying genetic variation contributing to adaptation to diverse environments, a 1001 Genomes Project to sequence geographically diverse A. thaliana strains has been initiated. Here we present the first phase of this project, based on population-scale sequencing of 80 strains drawn from eight regions throughout the species' native range. We describe the majority of common small-scale polymorphisms as well as many larger insertions and deletions in the A. thaliana pan-genome, their effects on gene function, and the patterns of local and global linkage among these variants. The action of processes other than spontaneous mutation is identified by comparing the spectrum of mutations that have accumulated since A. thaliana diverged from its closest relative 10 million years ago with the spectrum observed in the laboratory. Recent species-wide selective sweeps are rare, and potentially deleterious mutations are more common in marginal populations. 相似文献
48.
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease 总被引:2,自引:0,他引:2
Barrett JC Hansoul S Nicolae DL Cho JH Duerr RH Rioux JD Brant SR Silverberg MS Taylor KD Barmada MM Bitton A Dassopoulos T Datta LW Green T Griffiths AM Kistner EO Murtha MT Regueiro MD Rotter JI Schumm LP Steinhart AH Targan SR Xavier RJ;NIDDK IBD Genetics Consortium Libioulle C Sandor C Lathrop M Belaiche J Dewit O Gut I Heath S Laukens D Mni M Rutgeerts P Van Gossum A Zelenika D Franchimont D Hugot JP de Vos M Vermeire S 《Nature genetics》2008,40(8):955-962
Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development. 相似文献
49.
Brown KM Macgregor S Montgomery GW Craig DW Zhao ZZ Iyadurai K Henders AK Homer N Campbell MJ Stark M Thomas S Schmid H Holland EA Gillanders EM Duffy DL Maskiell JA Jetann J Ferguson M Stephan DA Cust AE Whiteman D Green A Olsson H Puig S Ghiorzo P Hansson J Demenais F Goldstein AM Gruis NA Elder DE Bishop JN Kefford RF Giles GG Armstrong BK Aitken JF Hopper JL Martin NG Trent JM Mann GJ Hayward NK 《Nature genetics》2008,40(7):838-840
We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases. 相似文献
50.
Tenesa A Farrington SM Prendergast JG Porteous ME Walker M Haq N Barnetson RA Theodoratou E Cetnarskyj R Cartwright N Semple C Clark AJ Reid FJ Smith LA Kavoussanakis K Koessler T Pharoah PD Buch S Schafmayer C Tepel J Schreiber S Völzke H Schmidt CO Hampe J Chang-Claude J Hoffmeister M Brenner H Wilkening S Canzian F Capella G Moreno V Deary IJ Starr JM Tomlinson IP Kemp Z Howarth K Carvajal-Carmona L Webb E Broderick P Vijayakrishnan J Houlston RS Rennert G Ballinger D Rozek L Gruber SB 《Nature genetics》2008,40(5):631-637
In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology. 相似文献