全文获取类型
收费全文 | 640篇 |
免费 | 1篇 |
国内免费 | 9篇 |
专业分类
系统科学 | 13篇 |
教育与普及 | 2篇 |
理论与方法论 | 6篇 |
现状及发展 | 76篇 |
研究方法 | 85篇 |
综合类 | 448篇 |
自然研究 | 20篇 |
出版年
2020年 | 2篇 |
2019年 | 6篇 |
2018年 | 7篇 |
2017年 | 3篇 |
2016年 | 6篇 |
2015年 | 3篇 |
2014年 | 4篇 |
2013年 | 8篇 |
2012年 | 52篇 |
2011年 | 83篇 |
2010年 | 10篇 |
2009年 | 3篇 |
2008年 | 33篇 |
2007年 | 42篇 |
2006年 | 42篇 |
2005年 | 44篇 |
2004年 | 72篇 |
2003年 | 75篇 |
2002年 | 56篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1971年 | 2篇 |
1970年 | 5篇 |
1969年 | 5篇 |
1968年 | 8篇 |
1967年 | 4篇 |
1966年 | 3篇 |
1965年 | 1篇 |
排序方式: 共有650条查询结果,搜索用时 17 毫秒
101.
102.
103.
Gardner MJ Shallom SJ Carlton JM Salzberg SL Nene V Shoaibi A Ciecko A Lynn J Rizzo M Weaver B Jarrahi B Brenner M Parvizi B Tallon L Moazzez A Granger D Fujii C Hansen C Pederson J Feldblyum T Peterson J Suh B Angiuoli S Pertea M Allen J Selengut J White O Cummings LM Smith HO Adams MD Venter JC Carucci DJ Hoffman SL Fraser CM 《Nature》2002,419(6906):531-534
The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35% of the 23-megabase P. falciparum genome. 相似文献
104.
105.
Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana 总被引:21,自引:0,他引:21
Lin X Kaul S Rounsley S Shea TP Benito MI Town CD Fujii CY Mason T Bowman CL Barnstead M Feldblyum TV Buell CR Ketchum KA Lee J Ronning CM Koo HL Moffat KS Cronin LA Shen M Pai G Van Aken S Umayam L Tallon LJ Gill JE Adams MD Carrera AJ Creasy TH Goodman HM Somerville CR Copenhaver GP Preuss D Nierman WC White O Eisen JA Salzberg SL Fraser CM Venter JC 《Nature》1999,402(6763):761-768
Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2. 相似文献
106.
Horlings HM Bergamaschi A Nordgard SH Kim YH Han W Noh DY Salari K Joosse SA Reyal F Lingjaerde OC Kristensen VN Børresen-Dale AL Pollack J van de Vijver MJ 《Nature genetics》2008,40(7):809; author reply 810-809; author reply 812
107.
Vermulst M Wanagat J Kujoth GC Bielas JH Rabinovitch PS Prolla TA Loeb LA 《Nature genetics》2008,40(4):392-394
Mitochondrial DNA (mtDNA) mutations are thought to have a causal role in many age-related pathologies. Here we identify mtDNA deletions as a driving force behind the premature aging phenotype of mitochondrial mutator mice, and provide evidence for a homology-directed DNA repair mechanism in mitochondria that is directly linked to the formation of mtDNA deletions. In addition, our results demonstrate that the rate at which mtDNA mutations reach phenotypic expression differs markedly among tissues, which may be an important factor in determining the tolerance of a tissue to random mitochondrial mutagenesis. 相似文献
108.
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes 总被引:1,自引:0,他引:1
Zeggini E Scott LJ Saxena R Voight BF Marchini JL Hu T de Bakker PI Abecasis GR Almgren P Andersen G Ardlie K Boström KB Bergman RN Bonnycastle LL Borch-Johnsen K Burtt NP Chen H Chines PS Daly MJ Deodhar P Ding CJ Doney AS Duren WL Elliott KS Erdos MR Frayling TM Freathy RM Gianniny L Grallert H Grarup N Groves CJ Guiducci C Hansen T Herder C Hitman GA Hughes TE Isomaa B Jackson AU Jørgensen T Kong A Kubalanza K Kuruvilla FG Kuusisto J Langenberg C Lango H Lauritzen T Li Y Lindgren CM 《Nature genetics》2008,40(5):638-645
Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D. 相似文献
109.
Haigis KM Kendall KR Wang Y Cheung A Haigis MC Glickman JN Niwa-Kawakita M Sweet-Cordero A Sebolt-Leopold J Shannon KM Settleman J Giovannini M Jacks T 《Nature genetics》2008,40(5):600-608
Kras is commonly mutated in colon cancers, but mutations in Nras are rare. We have used genetically engineered mice to determine whether and how these related oncogenes regulate homeostasis and tumorigenesis in the colon. Expression of K-Ras(G12D) in the colonic epithelium stimulated hyperproliferation in a Mek-dependent manner. N-Ras(G12D) did not alter the growth properties of the epithelium, but was able to confer resistance to apoptosis. In the context of an Apc-mutant colonic tumor, activation of K-Ras led to defects in terminal differentiation and expansion of putative stem cells within the tumor epithelium. This K-Ras tumor phenotype was associated with attenuated signaling through the MAPK pathway, and human colon cancer cells expressing mutant K-Ras were hypersensitive to inhibition of Raf, but not Mek. These studies demonstrate clear phenotypic differences between mutant Kras and Nras, and suggest that the oncogenic phenotype of mutant K-Ras might be mediated by noncanonical signaling through Ras effector pathways. 相似文献
110.
Bentley DR Balasubramanian S Swerdlow HP Smith GP Milton J Brown CG Hall KP Evers DJ Barnes CL Bignell HR Boutell JM Bryant J Carter RJ Keira Cheetham R Cox AJ Ellis DJ Flatbush MR Gormley NA Humphray SJ Irving LJ Karbelashvili MS Kirk SM Li H Liu X Maisinger KS Murray LJ Obradovic B Ost T Parkinson ML Pratt MR Rasolonjatovo IM Reed MT Rigatti R Rodighiero C Ross MT Sabot A Sankar SV Scally A Schroth GP Smith ME Smith VP Spiridou A Torrance PE Tzonev SS Vermaas EH Walter K Wu X Zhang L Alam MD 《Nature》2008,456(7218):53-59
DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications. 相似文献