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   4241篇
  免费   349篇
  2023年   14篇
  2022年   33篇
  2021年   63篇
  2020年   33篇
  2019年   54篇
  2018年   67篇
  2017年   62篇
  2016年   84篇
  2015年   179篇
  2014年   160篇
  2013年   241篇
  2012年   307篇
  2011年   296篇
  2010年   212篇
  2009年   174篇
  2008年   285篇
  2007年   288篇
  2006年   253篇
  2005年   225篇
  2004年   251篇
  2003年   271篇
  2002年   245篇
  2001年   44篇
  2000年   35篇
  1999年   48篇
  1998年   77篇
  1997年   42篇
  1996年   50篇
  1995年   43篇
  1994年   50篇
  1993年   40篇
  1992年   29篇
  1991年   24篇
  1990年   17篇
  1989年   16篇
  1988年   23篇
  1987年   19篇
  1986年   13篇
  1985年   21篇
  1984年   24篇
  1983年   14篇
  1982年   30篇
  1981年   23篇
  1980年   21篇
  1979年   12篇
  1978年   12篇
  1977年   11篇
  1976年   7篇
  1974年   9篇
  1973年   7篇
排序方式: 共有4590条查询结果,搜索用时 31 毫秒
981.
Under projections of global climate change and other stressors, significant changes in the ecology, structure and function of coral reefs are predicted. Current management strategies tend to look to the past to set goals, focusing on halting declines and restoring baseline conditions. Here, we explore a complementary approach to decision making that is based on the anticipation of future changes in ecosystem state, function and services. Reviewing the existing literature and utilizing a scenario planning approach, we explore how the structure of coral reef communities might change in the future in response to global climate change and overfishing. We incorporate uncertainties in our predictions by considering heterogeneity in reef types in relation to structural complexity and primary productivity. We examine 14 ecosystem services provided by reefs, and rate their sensitivity to a range of future scenarios and management options. Our predictions suggest that the efficacy of management is highly dependent on biophysical characteristics and reef state. Reserves are currently widely used and are predicted to remain effective for reefs with high structural complexity. However, when complexity is lost, maximizing service provision requires a broader portfolio of management approaches, including the provision of artificial complexity, coral restoration, fish aggregation devices and herbivore management. Increased use of such management tools will require capacity building and technique refinement and we therefore conclude that diversification of our management toolbox should be considered urgently to prepare for the challenges of managing reefs into the 21st century.  相似文献   
982.
983.
The invasive multicolored Asian ladybeetle, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), aggregates inside dwellings during winter to avoid cold weather. This adaptive behavior disturbs homeowners, because of the large numbers of individuals that aggregate, which induces allergic reactions. The migratory flight patterns of this species have been well documented, with individuals preferentially moving toward prominent and high color contrast elements. However, the factors involved in the selection of aggregation sites by this species have yet to be elucidated. Here, we evaluated the influence of (i) the density of individuals and (ii) the type of available shelters on decisions by H. axyridis to settle and aggregate under shelters. A dual choice bioassay conducted in the laboratory demonstrated the presence of mutual attraction to conspecifics. We also found that individuals preferentially settled under red covered shelters compared to transparent shelters, and that the type of shelter outweighed the effect of social interactions among conspecifics. Moreover, this experiment was performed under non‐wintering conditions, providing the first evidence that aggregative behavior in this species can also occur under those specific conditions.  相似文献   
984.
This study investigates the dynamics of zymogen activation when both extrinsic tenase and prothrombinase are assembled on an appropriate membrane. Although the activation of prothrombin by surface-localized prothrombinase is clearly mediated by flow-induced dilutional effects, we find that when factor X is activated in isolation by surface-localized extrinsic tenase, it exhibits characteristics of diffusion-mediated activation in which diffusion of substrate to the catalytically active region is rate-limiting. When prothrombin and factor X are activated coincident with each other, competition for available membrane binding sites masks the diffusion-limiting effects of factor X activation. To verify the role of membrane binding in the activation of factor X by extrinsic tenase under flow conditions, we demonstrate that bovine lactadherin competes for both factor X and Xa binding sites, limiting factor X activation and forcing the release of bound factor Xa from the membrane at a venous shear rate (100 s(-1)). Finally, we present steady-state models of prothrombin and factor X activation under flow showing that zymogen and enzyme membrane binding events further regulate the coagulation process in an open system representative of the vasculature geometry.  相似文献   
985.
Recent years have witnessed a breathtaking increase in the availability of genome sequence data, providing evidence of the highly duplicate nature of eukaryotic genomes. Plants are exceptional among eukaryotic organisms in that duplicate loci compose a large fraction of their genomes, partly because of the frequent occurrence of polyploidy (or whole-genome duplication) events. Tandem gene duplication and transposition have also contributed to the large number of duplicated genes in plant genomes. Evolutionary analyses allowed the dynamics of duplicate gene evolution to be studied and several models were proposed. It seems that, over time, many duplicated genes were lost and some of those that were retained gained new functions and/or expression patterns (neofunctionalization) or subdivided their functions and/or expression patterns between them (subfunctionalization). Recent studies have provided examples of genes that originated by duplication with successive diversification within plants. In this review, we focused on the TEL (TERMINAL EAR1-like) genes to illustrate such mechanisms. Emerged from the mei2 gene family, these TEL genes are likely to be land plant-specific. Phylogenetic analyses revealed one or two TEL copies per diploid genome. TEL gene degeneration and loss in several Angiosperm species such as in poplar and maize seem to have occurred. In Arabidopsis thaliana, whose genome experienced at least three polyploidy events followed by massive gene loss and genomic reorganization, two TEL genes were retained and two new shorter TEL-like (MCT) genes emerged. Molecular and expression analyses suggest for these genes sub- and neofunctionalization events, but confirmation will come from their functional characterization.  相似文献   
986.
A 378-bp section of the mitochondrial displacement loop was used to estimate genetic diversity in the native Canadian equine populations. The inclusion of 10 Mountain and Moorland, 3 Nordic pony breeds, 2 feral populations, and 5 horse breeds were also investigated as they may have influenced the development (or rejuvenation) of the native Canadian populations. A total of 281 samples were sequenced, which produced 75 haplotypes derived from 54 informative sites. On further investigation, 36 of these 75 haplotypes were found to be previously unreported. Overall, total diversity was lowest in the feral Sable Island population with a haplotype diversity (0.27 ± 0.12), nucleotide diversity (0.0007 ± 0.0004), and pairwise difference of 0.286 ± 0.317. This is not surprising due to the geographic isolation of this population. Haplotype diversity was highest (1.00 ± 0.13) in the New Forest population, pairwise difference was highest (8.061 ± 4.028) in the Icelandic breed, whereas nucleotide diversity was highest in the Exmoor breed (0.0209 ± 0.0025). Within the Canadian populations, haplotype diversity was highest in the Newfoundland pony (0.96 ± 0.08), whereas pairwise difference and nucleotide diversity was highest in the Canadian horse (7.090 ± 3.581 and 0.0188 ± 0.0042, respectively). Three different estimates of genetic distances were used to examine the phylogenetic relationships amongst these populations. All 3 estimates produced similar topologies. In general, the native Canadian populations were highly represented in the D clade, with particular emphasis in the D1 and D2 clades. This is an important factor when considering the phylogenetic conservation of these Canadian equine populations.  相似文献   
987.
Honey bee colonies (Apis mellifera) have been selected for low level of Nosema in Denmark over decades and Nosema is now rarely found in bee colonies from these breeding lines. We compared the immune response of a selected and an unselected honey bee lineage, taking advantage of the haploid males to study its potential impact on the tolerance toward Nosema ceranae, a novel introduced microsporidian pathogen. After artificial infections of the N. ceranae spores, the lineage selected for Nosema tolerance showed a higher N. ceranae spore load, a lower mortality and an up-regulated immune response. The differences in the response of the innate immune system between the selected and unselected lineage were strongest at day six post infection. In particular genes of the Toll pathway were up-regulated in the selected strain, probably is the main immune pathway involved in N. ceranae infection response. After decades of selective breeding for Nosema tolerance in the Danish strain, it appears these bees are tolerant to N. ceranae infections.  相似文献   
988.
Antibodies and prorenin mutants have long been used to structurally characterize prorenin, the inactive proenzyme form of renin. They were designed on the basis of homology models built using other aspartyl protease proenzyme structures since no structure was available for prorenin. Here, we present the first X-ray structure of a prorenin. The current structure of prorenin reveals that, in this zymogene, the active site of renin is blocked by the N-terminal residues of the mature version of the renin molecule, which are, in turn, covered by an Ω-shaped prosegment. This prevents access of substrates to the active site. The departure of the prosegment on activation induces an important global conformational change in the mature renin molecule with respect to prorenin: similar to other related enzymes such as pepsin or gastricsin, the segment that constitutes the N-terminal β-strand in renin is displaced from the renin active site by about 180° straight into the position that corresponds to the N-terminal β-strand of the prorenin prosegment. This way, the renin active site will become completely exposed and capable of carrying out its catalytic functions. A unique inactivation mechanism is also revealed, which does not make use of a lysine against the catalytic aspartates, probably in order to facilitate pH-independent activation [e.g., by the (pro)renin receptor].  相似文献   
989.
The Old World scorpion Androctonus australis hector (Aah) produces one of the most lethal venoms for humans. Peptidic α-toxins AahI to AahIV are responsible for its potency, with AahII accounting for half of it. All four toxins are high affinity blockers of the fast inactivation phase of mammalian voltage-activated Na(+) channels. However, the high antigenic polymorphism of α-toxins prevents production of a polyvalent neutralizing antiserum, whereas the determinants dictating their trapping by neutralizing antibodies remain elusive. From an anti-AahII mAb, we generated an antigen binding fragment (Fab) with high affinity and selectivity for AahII and solved a 2.3 ?-resolution crystal structure of the complex. Sequestering of the C-terminal region of the bound toxin within a groove formed by the Fab combining loops is associated with a toxin orientation and main and side chain conformations that dictate the AahII antigenic specificity and efficient neutralization. From an anti-AahI mAb, we also preformed and crystallized a high affinity AahI-Fab complex. The 1.6 ?-resolution structure solved revealed a Fab molecule devoid of a bound AahI and with combining loops involved in packing interactions, denoting expulsion of the bound antigen upon crystal formation. Comparative analysis of the groove-like combining site of the toxin-bound anti-AahII Fab and planar combining surface of the unbound anti-AahI Fab along with complementary data from a flexible docking approach suggests occurrence of distinctive trapping orientations for the two toxins relative to their respective Fab. This study provides complementary templates for designing new molecules aimed at capturing Aah α-toxins and suitable for immunotherapy.  相似文献   
990.
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs topoisomerase I cleavage complexes (Top1cc) by hydrolyzing their 3'-phosphotyrosyl DNA bonds and repairs bleomycin-induced DNA damage by hydrolyzing 3'-phosphoglycolates. Yeast Tdp1 has also been implicated in the repair of topoisomerase II-DNA cleavage complexes (Top2cc). To determine whether vertebrate Tdp1 is involved in the repair of various DNA end-blocking lesions, we generated Tdp1 knock-out cells in chicken DT40 cells (Tdp1-/-) and Tdp1-complemented DT40 cells with human TDP1. We found that Tdp1-/- cells were not only hypersensitive to camptothecin and bleomycin but also to etoposide, methyl methanesulfonate (MMS), H(2)O(2), and ionizing radiation. We also show they were deficient in mitochondrial Tdp1 activity. In biochemical assays, recombinant human TDP1 was found to process 5'-phosphotyrosyl DNA ends when they mimic the 5'-overhangs of Top2cc. Tdp1 also processes 3'-deoxyribose phosphates generated from hydrolysis of abasic sites, which is consistent with the hypersensitivity of Tdp1-/- cells to MMS and H(2)O(2). Because recent studies established that CtIP together with BRCA1 also repairs topoisomerase-mediated DNA damage, we generated dual Tdp1-CtIP-deficient DT40 cells. Our results show that Tdp1 and CtIP act in parallel pathways for the repair of Top1cc and MMS-induced lesions but are epistatic for Top2cc. Together, our findings reveal a broad involvement of Tdp1 in DNA repair and clarify the role of human TDP1 in the repair of Top2-induced DNA damage.  相似文献   
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