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801.
Reich D Patterson N De Jager PL McDonald GJ Waliszewska A Tandon A Lincoln RR DeLoa C Fruhan SA Cabre P Bera O Semana G Kelly MA Francis DA Ardlie K Khan O Cree BA Hauser SL Oksenberg JR Hafler DA 《Nature genetics》2005,37(10):1113-1118
Multiple sclerosis is a common disease with proven heritability, but, despite large-scale attempts, no underlying risk genes have been identified. Traditional linkage scans have so far identified only one risk haplotype for multiple sclerosis (at HLA on chromosome 6), which explains only a fraction of the increased risk to siblings. Association scans such as admixture mapping have much more power, in principle, to find the weak factors that must explain most of the disease risk. We describe here the first high-powered admixture scan, focusing on 605 African American cases and 1,043 African American controls, and report a locus on chromosome 1 that is significantly associated with multiple sclerosis. 相似文献
802.
Lincoln MR Montpetit A Cader MZ Saarela J Dyment DA Tiislar M Ferretti V Tienari PJ Sadovnick AD Peltonen L Ebers GC Hudson TJ 《Nature genetics》2005,37(10):1108-1112
Genetic susceptibility to multiple sclerosis is associated with genes of the major histocompatibility complex (MHC), particularly HLA-DRB1 and HLA-DQB1 (ref. 1). Both locus and allelic heterogeneity have been reported in this genomic region. To clarify whether HLA-DRB1 itself, nearby genes in the region encoding the MHC or combinations of these loci underlie susceptibility to multiple sclerosis, we genotyped 1,185 Canadian and Finnish families with multiple sclerosis (n = 4,203 individuals) with a high-density SNP panel spanning the genes encoding the MHC and flanking genomic regions. Strong associations in Canadian and Finnish samples were observed with blocks in the HLA class II genomic region (P < 4.9 x 10(-13) and P < 2.0 x 10(-16), respectively), but the strongest association was with HLA-DRB1 (P < 4.4 x 10(-17)). Conditioning on either HLA-DRB1 or the most significant HLA class II haplotype block found no additional block or SNP association independent of the HLA class II genomic region. This study therefore indicates that MHC-associated susceptibility to multiple sclerosis is determined by HLA class II alleles, their interactions and closely neighboring variants. 相似文献
803.
Prawitt D Enklaar T Gärtner-Rupprecht B Spangenberg C Lausch E Reutzel D Fees S Korzon M Brozek I Limon J Housman DE Pelletier J Zabel B 《Nature genetics》2005,37(8):785-6; author reply 786-7
804.
Efficiency and power in genetic association studies 总被引:30,自引:0,他引:30
de Bakker PI Yelensky R Pe'er I Gabriel SB Daly MJ Altshuler D 《Nature genetics》2005,37(11):1217-1223
We investigated selection and analysis of tag SNPs for genome-wide association studies by specifically examining the relationship between investment in genotyping and statistical power. Do pairwise or multimarker methods maximize efficiency and power? To what extent is power compromised when tags are selected from an incomplete resource such as HapMap? We addressed these questions using genotype data from the HapMap ENCODE project, association studies simulated under a realistic disease model, and empirical correction for multiple hypothesis testing. We demonstrate a haplotype-based tagging method that uniformly outperforms single-marker tests and methods for prioritization that markedly increase tagging efficiency. Examining all observed haplotypes for association, rather than just those that are proxies for known SNPs, increases power to detect rare causal alleles, at the cost of reduced power to detect common causal alleles. Power is robust to the completeness of the reference panel from which tags are selected. These findings have implications for prioritizing tag SNPs and interpreting association studies. 相似文献
805.
Metastatic potential as a heritable trait 总被引:2,自引:0,他引:2
Threadgill DW 《Nature genetics》2005,37(10):1026-1027
806.
Yen AS Gellert R Schröder C Morris RV Bell JF Knudson AT Clark BC Ming DW Crisp JA Arvidson RE Blaney D Brückner J Christensen PR DesMarais DJ de Souza PA Economou TE Ghosh A Hahn BC Herkenhoff KE Haskin LA Hurowitz JA Joliff BL Johnson JR Klingelhöfer G Madsen MB McLennan SM McSween HY Richter L Rieder R Rodionov D Soderblom L Squyres SW Tosca NJ Wang A Wyatt M Zipfel J 《Nature》2005,436(7047):49-54
The mineralogical and elemental compositions of the martian soil are indicators of chemical and physical weathering processes. Using data from the Mars Exploration Rovers, we show that bright dust deposits on opposite sides of the planet are part of a global unit and not dominated by the composition of local rocks. Dark soil deposits at both sites have similar basaltic mineralogies, and could reflect either a global component or the general similarity in the compositions of the rocks from which they were derived. Increased levels of bromine are consistent with mobilization of soluble salts by thin films of liquid water, but the presence of olivine in analysed soil samples indicates that the extent of aqueous alteration of soils has been limited. Nickel abundances are enhanced at the immediate surface and indicate that the upper few millimetres of soil could contain up to one per cent meteoritic material. 相似文献
807.
Haskin LA Wang A Jolliff BL McSween HY Clark BC Des Marais DJ McLennan SM Tosca NJ Hurowitz JA Farmer JD Yen A Squyres SW Arvidson RE Klingelhöfer G Schröder C de Souza PA Ming DW Gellert R Zipfel J Brückner J Bell JF Herkenhoff K Christensen PR Ruff S Blaney D Gorevan S Cabrol NA Crumpler L Grant J Soderblom L 《Nature》2005,436(7047):66-69
Gusev crater was selected as the landing site for the Spirit rover because of the possibility that it once held a lake. Thus one of the rover's tasks was to search for evidence of lake sediments. However, the plains at the landing site were found to be covered by a regolith composed of olivine-rich basaltic rock and windblown 'global' dust. The analyses of three rock interiors exposed by the rock abrasion tool showed that they are similar to one another, consistent with having originated from a common lava flow. Here we report the investigation of soils, rock coatings and rock interiors by the Spirit rover from sol (martian day) 1 to sol 156, from its landing site to the base of the Columbia hills. The physical and chemical characteristics of the materials analysed provide evidence for limited but unequivocal interaction between water and the volcanic rocks of the Gusev plains. This evidence includes the softness of rock interiors that contain anomalously high concentrations of sulphur, chlorine and bromine relative to terrestrial basalts and martian meteorites; sulphur, chlorine and ferric iron enrichments in multilayer coatings on the light-toned rock Mazatzal; high bromine concentration in filled vugs and veins within the plains basalts; positive correlations between magnesium, sulphur and other salt components in trench soils; and decoupling of sulphur, chlorine and bromine concentrations in trench soils compared to Gusev surface soils, indicating chemical mobility and separation. 相似文献
808.
Wilson D Aster R West M Ni J Grand S Gao W Baldridge WS Semken S Patel P 《Nature》2005,433(7028):851-855
A high-resolution, regional passive seismic experiment in the Rio Grande rift region of the southwestern United States has produced new images of upper-mantle velocity structure and crust-mantle topography. Synthesizing these results with geochemical and other geophysical evidence reveals highly symmetric lower-crustal and upper-mantle lithosphere extensional deformation, suggesting a pure-shear rifting mechanism for the Rio Grande rift. Extension in the lower crust is distributed over a region four times the width of the rift's surface expression. Here we propose that the laterally distributed, pure shear extension is a combined effect of low strain rate and a regionally elevated geotherm, possibly abetted by pre-existing lithospheric structures, at the time of rift initiation. Distributed extension in the lower crust and mantle has induced less concentrated vertical mantle upwelling and less vigorous small-scale convection than would have arisen from more localized deformation. This lack of highly focused mantle upwelling may explain a deficit of rift-related volcanics in the Rio Grande rift compared to other major rift systems such as the Kenya rift. 相似文献
809.
Loftus B Anderson I Davies R Alsmark UC Samuelson J Amedeo P Roncaglia P Berriman M Hirt RP Mann BJ Nozaki T Suh B Pop M Duchene M Ackers J Tannich E Leippe M Hofer M Bruchhaus I Willhoeft U Bhattacharya A Chillingworth T Churcher C Hance Z Harris B Harris D Jagels K Moule S Mungall K Ormond D Squares R Whitehead S Quail MA Rabbinowitsch E Norbertczak H Price C Wang Z Guillén N Gilchrist C Stroup SE Bhattacharya S Lohia A Foster PG Sicheritz-Ponten T Weber C Singh U Mukherjee C El-Sayed NM 《Nature》2005,433(7028):865-868
Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen. 相似文献
810.
Hornstein E Mansfield JH Yekta S Hu JK Harfe BD McManus MT Baskerville S Bartel DP Tabin CJ 《Nature》2005,438(7068):671-674