首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2405篇
  免费   77篇
  2482篇
  2024年   38篇
  2023年   35篇
  2022年   70篇
  2021年   143篇
  2020年   78篇
  2019年   90篇
  2018年   85篇
  2017年   66篇
  2016年   110篇
  2015年   142篇
  2014年   184篇
  2013年   163篇
  2012年   191篇
  2011年   197篇
  2010年   104篇
  2009年   81篇
  2008年   116篇
  2007年   97篇
  2006年   83篇
  2005年   89篇
  2004年   81篇
  2003年   68篇
  2002年   48篇
  2001年   7篇
  2000年   12篇
  1999年   8篇
  1998年   7篇
  1997年   9篇
  1996年   9篇
  1995年   3篇
  1994年   5篇
  1993年   2篇
  1992年   7篇
  1991年   4篇
  1990年   5篇
  1988年   3篇
  1987年   2篇
  1983年   2篇
  1982年   2篇
  1981年   5篇
  1980年   4篇
  1978年   2篇
  1976年   2篇
  1974年   2篇
  1971年   2篇
  1968年   2篇
  1967年   3篇
  1966年   2篇
  1965年   2篇
  1902年   1篇
排序方式: 共有2482条查询结果,搜索用时 15 毫秒
1.
2.
This study compares estimates of the census size of the spawning population with genetic estimates of effective current and long-term population size for an abundant and commercially important marine invertebrate, the brown tiger prawn (Penaeus esculentus). Our aim was to focus on the relationship between genetic effective and census size that may provide a source of information for viability analyses of naturally occurring populations. Samples were taken in 2001, 2002 and 2003 from a population on the east coast of Australia and temporal allelic variation was measured at eight polymorphic microsatellite loci. Moments-based and maximum-likelihood estimates of current genetic effective population size ranged from 797 to 1304. The mean long-term genetic effective population size was 9968. Although small for a large population, the effective population size estimates were above the threshold where genetic diversity is lost at neutral alleles through drift or inbreeding. Simulation studies correctly predicted that under these experimental conditions the genetic estimates would have non-infinite upper confidence limits and revealed they might be overestimates of the true size. We also show that estimates of mortality and variance in family size may be derived from data on average fecundity, current genetic effective and census spawning population size, assuming effective population size is equivalent to the number of breeders. This work confirms that it is feasible to obtain accurate estimates of current genetic effective population size for abundant Type III species using existing genetic marker technology.  相似文献   
3.
Roosild TP  Miller S  Booth IR  Choe S 《Cell》2002,109(6):781-791
The regulation of cation content is critical for cell growth. However, the molecular mechanisms that gate the systems that control K+ movements remain unclear. KTN is a highly conserved cytoplasmic domain present ubiquitously in a variety of prokaryotic and eukaryotic K+ channels and transporters. Here we report crystal structures for two representative KTN domains that reveal a dimeric hinged assembly. Alternative ligands NAD+ and NADH block or vacate, respectively, the hinge region affecting the dimer's conformational flexibility. Conserved, surface-exposed hydrophobic patches that become coplanar upon hinge closure provide an assembly interface for KTN tetramerization. Mutational analysis using the KefC system demonstrates that this domain directly interacts with its respective transmembrane constituent, coupling ligand-mediated KTN conformational changes to the permease's activity.  相似文献   
4.
ATIC encompasses both AICAR transformylase and IMP cyclohydrolase activities that are responsible for the catalysis of the penultimate and final steps of the purine de novo synthesis pathway. The formyl transfer reaction catalyzed by the AICAR Tfase domain is substantially more demanding than that catalyzed by the other folate-dependent enzyme of the purine biosynthesis pathway, GAR transformylase. Identification of the AICAR Tfase active site and key catalytic residues is essential to elucidate how the non-nucleophilic AICAR amino group is activated for formyl transfer. Hence, the crystal structure of dimeric avian ATIC was determined as a complex with the AICAR Tfase substrate AICAR, as well as with an IMP cyclohydrolase inhibitor, XMP, to 1.93 A resolution. AICAR is bound at the dimer interface of the transformylase domains and forms an extensive hydrogen bonding network with a multitude of active site residues. The crystal structure suggests that the conformation of the 4-carboxamide of AICAR is poised to increase the nucleophilicity of the C5 amine, while proton abstraction occurs via His(268) concomitant with formyl transfer. Lys(267) is likely to be involved in the stabilization of the anionic formyl transfer transition state and in subsequent protonation of the THF leaving group.  相似文献   
5.
    
Sixteen fluorescent analogues of the lipid-soluble antioxidant vitamin alpha-tocopherol were prepared incorporating fluorophores at the terminus of omega-functionalized 2-n-alkyl-substituted chromanols (1a-d and 4a-d) that match the methylation pattern of alpha-tocopherol, the most biologically active form of vitamin E. The fluorophores used include 9-anthroyloxy (AO), 7-nitrobenz-2-oxa-1,3-diazole (NBD), N-methyl anthranilamide (NMA), and dansyl (DAN). The compounds were designed to function as fluorescent reporter ligands for protein-binding and lipid transfer assays. The fluorophores were chosen to maximize the fluorescence changes observed upon moving from an aqueous environment (low fluorescence intensity) to an hydrophobic environment such as a protein's binding site (high fluorescence intensity). Compounds 9d (anthroyloxy) and 10d (nitrobenzoxadiazole), having a C9-carbon chain between the chromanol and the fluorophore, were shown to bind specifically and reversibly to recombinant human tocopherol transfer protein (alpha-TTP) with dissociation constants of approximately 280 and 60 nM, respectively, as compared to 25 nM for the natural ligand 2R,4'R,8'R-alpha-tocopherol. Thus, compounds have been prepared that allow the investigation of the rate of alpha-TTP-mediated inter-membrane transfer of alpha-tocopherol and to investigate the mechanism of alpha-TTP function at membranes of different composition.  相似文献   
6.
Habitat loss and hunting threaten bonobos (Pan paniscus), Endangered (IUCN) great apes endemic to lowland rainforests of the Democratic Republic of Congo. Conservation planning requires a current, data-driven, rangewide map of probable bonobo distribution and an understanding of key attributes of areas used by bonobos. We present a rangewide suitability model for bonobos based on a maximum entropy algorithm in which data associated with locations of bonobo nests helped predict suitable conditions across the species’ entire range. We systematically evaluated available biotic and abiotic factors, including a bonobo-specific forest fragmentation layer (forest edge density), and produced a final model revealing the importance of simple threat-based factors in a data poor environment. We confronted the issue of survey bias in presence-only models and devised a novel evaluation approach applicable to other taxa by comparing models built with data from geographically distinct sub-regions that had higher survey effort. The model’s classification accuracy was high (AUC = 0.82). Distance from agriculture and forest edge density best predicted bonobo occurrence with bonobo nests more likely to occur farther from agriculture and in areas of lower edge density. These results suggest that bonobos either avoid areas of higher human activity, fragmented forests, or both, and that humans reduce the effective habitat of bonobos. The model results contribute to an increased understanding of threats to bonobo populations, as well as help identify priority areas for future surveys and determine core bonobo protection areas.  相似文献   
7.
    
Hydrogels capable of gene delivery provide a combinatorial approach for nerve regeneration, with the hydrogel supporting neurite outgrowth and gene delivery inducing the expression of inductive factors. This report investigates the design of hydrogels that balance the requirements for supporting neurite growth with those requirements for promoting gene delivery. Enzymatically-degradable PEG hydrogels encapsulating dorsal root ganglia explants, fibroblasts, and lipoplexes encoding nerve growth factor were gelled within channels that can physically guide neurite outgrowth. Transfection of fibroblasts increased with increasing concentration of Arg-Gly-Asp (RGD) cell adhesion sites and decreasing PEG content. The neurite length increased with increasing RGD concentration within 10% PEG hydrogels, yet was maximal within 7.5% PEG hydrogels at intermediate RGD levels. Delivering lipoplexes within the gel produced longer neurites than culture in NGF-supplemented media or co-culture with cells exposed to DNA prior to encapsulation. Hydrogels designed to support neurite outgrowth and deliver gene therapy vectors locally may ultimately be employed to address multiple barriers that limit regeneration.  相似文献   
8.
    
During cytokinesis a new crosswall is rapidly laid down. This process involves the formation at the cell equator of a tubulo‐vesicular membrane network (TVN). This TVN evolves into a tubular network (TN) and a planar fenestrated sheet, which extends at its periphery before fusing to the mother cell wall. The role of cell wall polymers in cell plate assembly is poorly understood. We used specific stains and GFP‐labelled cellulose synthases (CESAs) to show that cellulose, as well as three distinct CESAs, accumulated in the cell plate already at the TVN stage. This early presence suggests that cellulose is extruded into the tubular membrane structures of the TVN. Co‐localisation studies using GFP–CESAs suggest the delivery of cellulose synthase complexes (CSCs) to the cell plate via phragmoplast‐associated vesicles. In the more mature TN part of the cell plate, we observed delivery of GFP–CESA from doughnut‐shaped organelles, presumably Golgi bodies. During the conversion of the TN into a planar fenestrated sheet, the GFP–CESA density diminished, whereas GFP–CESA levels remained high in the TVN zone at the periphery of the expanding cell plate. We observed retrieval of GFP–CESA in clathrin‐containing structures from the central zone of the cell plate and from the plasma membrane of the mother cell, which may contribute to the recycling of CESAs to the peripheral growth zone of the cell plate. These observations, together with mutant phenotypes of cellulose‐deficient mutants and pharmacological experiments, suggest a key role for cellulose synthesis already at early stages of cell plate assembly.  相似文献   
9.
    
ABSTRACT

This study assessed sleep quality, sleepiness and use of workplace break opportunities in 1285 health-care workers via an online questionnaire. Two hospitals were surveyed – one with and one without a fatigue mitigation policy. Across all respondents, 68.9% reported generally taking breaks of at least 30 min and 21.7% had access to a quiet place to rest, with no significant differences between hospitals. The presence of a fatigue mitigation policy was not associated with reduced sleepiness. However, accounting for hospital and shift characteristics, employees with access to a quiet place to rest while on break had significantly lower self-reported sleepiness scores.  相似文献   
10.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号