全文获取类型
收费全文 | 913篇 |
免费 | 221篇 |
国内免费 | 252篇 |
专业分类
系统科学 | 82篇 |
丛书文集 | 5篇 |
教育与普及 | 11篇 |
理论与方法论 | 2篇 |
现状及发展 | 21篇 |
研究方法 | 81篇 |
综合类 | 1184篇 |
出版年
2024年 | 13篇 |
2023年 | 32篇 |
2022年 | 34篇 |
2021年 | 34篇 |
2020年 | 5篇 |
2019年 | 11篇 |
2018年 | 38篇 |
2017年 | 27篇 |
2016年 | 33篇 |
2015年 | 30篇 |
2014年 | 97篇 |
2013年 | 57篇 |
2012年 | 77篇 |
2011年 | 72篇 |
2010年 | 49篇 |
2009年 | 35篇 |
2008年 | 80篇 |
2007年 | 108篇 |
2006年 | 82篇 |
2005年 | 81篇 |
2004年 | 119篇 |
2003年 | 82篇 |
2002年 | 42篇 |
2001年 | 47篇 |
2000年 | 38篇 |
1999年 | 14篇 |
1998年 | 15篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 6篇 |
1993年 | 6篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1985年 | 2篇 |
1984年 | 1篇 |
排序方式: 共有1386条查询结果,搜索用时 32 毫秒
941.
Nusbaum C Zody MC Borowsky ML Kamal M Kodira CD Taylor TD Whittaker CA Chang JL Cuomo CA Dewar K FitzGerald MG Yang X Abouelleil A Allen NR Anderson S Bloom T Bugalter B Butler J Cook A DeCaprio D Engels R Garber M Gnirke A Hafez N Hall JL Norman CH Itoh T Jaffe DB Kuroki Y Lehoczky J Lui A Macdonald P Mauceli E Mikkelsen TS Naylor JW Nicol R Nguyen C Noguchi H O'Leary SB O'Neill K Piqani B Smith CL Talamas JA Topham K Totoki Y Toyoda A Wain HM Young SK Zeng Q Zimmer AR Fujiyama A Hattori M 《Nature》2005,437(7058):551-555
Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements. 相似文献
942.
Kim S Poursine-Laurent J Truscott SM Lybarger L Song YJ Yang L French AR Sunwoo JB Lemieux S Hansen TH Yokoyama WM 《Nature》2005,436(7051):709-713
Self versus non-self discrimination is a central theme in biology from plants to vertebrates, and is particularly relevant for lymphocytes that express receptors capable of recognizing self-tissues and foreign invaders. Comprising the third largest lymphocyte population, natural killer (NK) cells recognize and kill cellular targets and produce pro-inflammatory cytokines. These potentially self-destructive effector functions can be controlled by inhibitory receptors for the polymorphic major histocompatibility complex (MHC) class I molecules that are ubiquitously expressed on target cells. However, inhibitory receptors are not uniformly expressed on NK cells, and are germline-encoded by a set of polymorphic genes that segregate independently from MHC genes. Therefore, how NK-cell self-tolerance arises in vivo is poorly understood. Here we demonstrate that NK cells acquire functional competence through 'licensing' by self-MHC molecules. Licensing involves a positive role for MHC-specific inhibitory receptors and requires the cytoplasmic inhibitory motif originally identified in effector responses. This process results in two types of self-tolerant NK cells--licensed or unlicensed--and may provide new insights for exploiting NK cells in immunotherapy. This self-tolerance mechanism may be more broadly applicable within the vertebrate immune system because related germline-encoded inhibitory receptors are widely expressed on other immune cells. 相似文献
943.
R gene expression induced by a type-III effector triggers disease resistance in rice 总被引:10,自引:0,他引:10
Gu K Yang B Tian D Wu L Wang D Sreekala C Yang F Chu Z Wang GL White FF Yin Z 《Nature》2005,435(7045):1122-1125
Disease resistance (R) genes in plants encode products that specifically recognise incompatible pathogens and trigger a cascade of events leading to disease resistance in the host plant. R-gene specificity is dictated by both host R genes and cognate avirulence (avr) genes in pathogens. However, the basis of gene-for-gene specificity is not well understood. Here, we report the cloning of the R gene Xa27 from rice and the cognate avr gene avrXa27 from Xanthomonas oryzae pv. oryzae. Resistant and susceptible alleles of Xa27 encode identical proteins. However, expression of only the resistant allele occurs when a rice plant is challenged by bacteria harbouring avrXa27, whose product is a nuclear localized type-III effector. Induction of Xa27 occurs only in the immediate vicinity of infected tissue, whereas ectopic expression of Xa27 resulted in resistance to otherwise compatible strains of the pathogen. Thus Xa27 specificity towards incompatible pathogens involves the differential expression of the R gene in the presence of the AvrXa27 effector. 相似文献
944.
Du W Bautista JF Yang H Diez-Sampedro A You SA Wang L Kotagal P Lüders HO Shi J Cui J Richerson GB Wang QK 《Nature genetics》2005,37(7):733-738
The large conductance calcium-sensitive potassium (BK) channel is widely expressed in many organs and tissues, but its in vivo physiological functions have not been fully defined. Here we report a genetic locus associated with a human syndrome of coexistent generalized epilepsy and paroxysmal dyskinesia on chromosome 10q22 and show that a mutation of the alpha subunit of the BK channel causes this syndrome. The mutant BK channel had a markedly greater macroscopic current. Single-channel recordings showed an increase in open-channel probability due to a three- to fivefold increase in Ca(2+) sensitivity. We propose that enhancement of BK channels in vivo leads to increased excitability by inducing rapid repolarization of action potentials, resulting in generalized epilepsy and paroxysmal dyskinesia by allowing neurons to fire at a faster rate. These results identify a gene that is mutated in generalized epilepsy and paroxysmal dyskinesia and have implications for the pathogenesis of human epilepsy, the neurophysiology of paroxysmal movement disorders and the role of BK channels in neurological disease. 相似文献
945.
Vogt G Chapgier A Yang K Chuzhanova N Feinberg J Fieschi C Boisson-Dupuis S Alcais A Filipe-Santos O Bustamante J de Beaucoudrey L Al-Mohsen I Al-Hajjar S Al-Ghonaium A Adimi P Mirsaeidi M Khalilzadeh S Rosenzweig S de la Calle Martin O Bauer TR Puck JM Ochs HD Furthner D Engelhorn C Belohradsky B Mansouri D Holland SM Schreiber RD Abel L Cooper DN Soudais C Casanova JL 《Nature genetics》2005,37(7):692-700
Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate. 相似文献
946.
Aluminum (A1) toxicity is the major factor limiting crop productivity in acid soils. In this study, a recombinant inbreed line (RIL) population derived from a cross between an A1 sensitive lowland indica rice variety IR1552 and an A1 tolerant upland japonica rice variety Azucena, was used for mapping quantitative trait loci (QTLs) for A1 tolerance. Three QTLs for relative root length (RRL) were detected on chromosome 1,9, 12, respectively, and 1 QTL for root length under A1 stress is identical on chromosome 1 after one week and two weeks stress. Comparison of QTLs on chromosome 1 from different studies indicated an identical interval between C86 and RZ801 with gene(s) for A1 tolerance. This interval provides an important start point for isolating genes responsible for A1 tolerance and understanding the genetic nature of Al tolerance in rice. Four A1 induced ESTs located in this interval were screened by reverse Northern analysis and confirmed by Northern analysis. They would be candidate genes for the QTL. 相似文献
947.
To evaluate the clinic outcome of off-pump coronary bypass grafting (OPCABG) of patients with coronary heart disease and chronic obstructive pulmonary disease, we collected and analyzed 1998-2002 data on 28 patients with these two diseases who had received off-pump coronary bypass operation in our hospital, and compared with data on those who also had the same two diseases but received on-pump coronary artery bypass at same time. There were no operation-related death;one died of respiratory failure 14 days after operation while staying in hospital; there were more respiratory complications in the conventional coronary artery bypass grafting group (CCABG) than in the OPCABG group; and the PaO2/FiO2 in the CCABG group was higher than that in the OPCABG group during operation because of CPB, but lower than that in the OPCABG group 6-12 hours after operation. OPCABG seemed more suitable than CCABG for coronary artery disease patients with chronic obstructive pulmonary disease due to less damage to their oxygen-exchange capability and the fewer respiratory complications. 相似文献
948.
In order to remove the low turbidity present in surface water, a novel metal-polysilicate coagulant was used to treat the raw water taken from Tanjiang River in Guangdong Province. This study on the effects of A1/Fe molar ratio on the performance of a complex compound formed by polysilicic acid, aluminium and ferric salt (PAFS) showed that PAFS with A1/Fe ratio of 10:3 seemed to have the best coagulation performance in removing turbidity and color. Experimental results showed that under the conditions of polymerization time of 15 d, sedimentation time of 12 min, and pH of 6-8,PAFS with A1/Fe molar ratio of 10:3 had the best coagulation efficiency and lowest residual A1 concentration. The turbidity decreased from 23.8 NTU to 3.23 NTU and the residual A1 concentration was only 0.165 mg/L in the product water. It could be speculated that colloidal impurities and particulate A1 were removed by adsorption bridging and electrical neutralization of long chain inorganic polymer coagulants. 相似文献
949.
Creation of reversed phase high-performance liquid chromatographic technique to assay platelet-activating factor 总被引:1,自引:0,他引:1
OBJECTIVE: To establish a new assay for platelet-activating factor (PAF), to compare it with bio-assay; and to discuss its significance in some elderly people diseases such as cerebral infarction and coronary heart disease. METHODS: To measure PAF levels in 100 controls, 23 elderly patients with cerebral infarction and 65 cases with coronary heart disease by reversed phase high-performance liquid chromatographic technique (rHPLC). RESULTS: rHPLC is more convenient, sensitive, specific, and less confusing, compared with bio-assay. The level of plasma PAF in patients with cerebral infarction was higher than that in the controls (P<0.01), and in patients with coronary heart disease. CONCLUSION: Detection of PAF with rHPLC is more reliable and more accurate. The new assay has important significance in PAF research. 相似文献
950.
Wallis JW Aerts J Groenen MA Crooijmans RP Layman D Graves TA Scheer DE Kremitzki C Fedele MJ Mudd NK Cardenas M Higginbotham J Carter J McGrane R Gaige T Mead K Walker J Albracht D Davito J Yang SP Leong S Chinwalla A Sekhon M Wylie K Dodgson J Romanov MN Cheng H de Jong PJ Osoegawa K Nefedov M Zhang H McPherson JD Krzywinski M Schein J Hillier L Mardis ER Wilson RK Warren WC 《Nature》2004,432(7018):761-764
Strategies for assembling large, complex genomes have evolved to include a combination of whole-genome shotgun sequencing and hierarchal map-assisted sequencing. Whole-genome maps of all types can aid genome assemblies, generally starting with low-resolution cytogenetic maps and ending with the highest resolution of sequence. Fingerprint clone maps are based upon complete restriction enzyme digests of clones representative of the target genome, and ultimately comprise a near-contiguous path of clones across the genome. Such clone-based maps are used to validate sequence assembly order, supply long-range linking information for assembled sequences, anchor sequences to the genetic map and provide templates for closing gaps. Fingerprint maps are also a critical resource for subsequent functional genomic studies, because they provide a redundant and ordered sampling of the genome with clones. In an accompanying paper we describe the draft genome sequence of the chicken, Gallus gallus, the first species sequenced that is both a model organism and a global food source. Here we present a clone-based physical map of the chicken genome at 20-fold coverage, containing 260 contigs of overlapping clones. This map represents approximately 91% of the chicken genome and enables identification of chicken clones aligned to positions in other sequenced genomes. 相似文献