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991.
Pattengale ND Aberer AJ Swenson KM Stamatakis A Moret BM 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2011,8(4):902-911
Many of the steps in phylogenetic reconstruction can be confounded by “rogue” taxa—taxa that cannot be placed with assurance anywhere within the tree, indeed, whose location within the tree varies with almost any choice of algorithm or parameters. Phylogenetic consensus methods, in particular, are known to suffer from this problem. In this paper, we provide a novel framework to define and identify rogue taxa. In this framework, we formulate a bicriterion optimization problem, the relative information criterion, that models the net increase in useful information present in the consensus tree when certain taxa are removed from the input data. We also provide an effective greedy heuristic to identify a subset of rogue taxa and use this heuristic in a series of experiments, with both pathological examples from the literature and a collection of large biological data sets. As the presence of rogue taxa in a set of bootstrap replicates can lead to deceivingly poor support values, we propose a procedure to recompute support values in light of the rogue taxa identified by our algorithm; applying this procedure to our biological data sets caused a large number of edges to move from “unsupported” to “supported” status, indicating that many existing phylogenies should be recomputed and reevaluated to reduce any inaccuracies introduced by rogue taxa. We also discuss the implementation issues encountered while integrating our algorithm into RAxML v7.2.7, particularly those dealing with scaling up the analyses. This integration enables practitioners to benefit from our algorithm in the analysis of very large data sets (up to 2,500 taxa and 10,000 trees, although we present the results of even larger analyses). 相似文献
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994.
Park KS Martelotto LG Peifer M Sos ML Karnezis AN Mahjoub MR Bernard K Conklin JF Szczepny A Yuan J Guo R Ospina B Falzon J Bennett S Brown TJ Markovic A Devereux WL Ocasio CA Chen JK Stearns T Thomas RK Dorsch M Buonamici S Watkins DN Peacock CD Sage J 《Nature medicine》2011,17(11):1504-1508
Small-cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer for which there is no effective treatment. Using a mouse model in which deletion of Rb1 and Trp53 in the lung epithelium of adult mice induces SCLC, we found that the Hedgehog signaling pathway is activated in SCLC cells independently of the lung microenvironment. Constitutive activation of the Hedgehog signaling molecule Smoothened (Smo) promoted the clonogenicity of human SCLC in vitro and the initiation and progression of mouse SCLC in vivo. Reciprocally, deletion of Smo in Rb1 and Trp53-mutant lung epithelial cells strongly suppressed SCLC initiation and progression in mice. Furthermore, pharmacological blockade of Hedgehog signaling inhibited the growth of mouse and human SCLC, most notably following chemotherapy. These findings show a crucial cell-intrinsic role for Hedgehog signaling in the development and maintenance of SCLC and identify Hedgehog pathway inhibition as a therapeutic strategy to slow the progression of disease and delay cancer recurrence in individuals with SCLC. 相似文献
995.
Dufour F Sasseville AM Chabaud S Massie B Siegel RM Langelier Y 《Apoptosis : an international journal on programmed cell death》2011,16(3):256-271
We previously reported that HSV-2 R1, the R1 subunit (ICP10; UL39) of herpes simplex virus type-2 ribonucleotide reductase, protects cells against apoptosis induced by the death receptor
(DR) ligands tumor necrosis factor-alpha- (TNFα) and Fas ligand (FasL) by interrupting DR-mediated signaling at, or upstream
of, caspase-8 activation. Further investigation of the molecular mechanism underlying HSV-2 R1 protection showed that extracellular-regulated
kinase 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI3-K)/Akt, NF-κB and JNK survival pathways do not play a major role in
this antiapoptotic function. Interaction studies revealed that HSV-2 R1 interacted constitutively with caspase-8. The HSV-2
R1 deletion mutant R1(1-834)-GFP and Epstein–Barr virus (EBV) R1, which did not protect against apoptosis induced by DR ligands,
did not interact with caspase-8, indicating that interaction is required for protection. HSV-2 R1 impaired caspase-8 activation
induced by caspase-8 over-expression, suggesting that interaction between the two proteins prevents caspase-8 dimerization/activation.
HSV-2 R1 bound to caspase-8 directly through its prodomain but did not interact with either its caspase domain or Fas-associated
death domain protein (FADD). Interaction between HSV-2 R1 and caspase-8 disrupted FADD-caspase-8 binding. We further demonstrated
that individually expressed HSV-1 R1 (ICP6) shares, with HSV-2 R1, the ability to bind caspase-8 and to protect cells against
DR-induced apoptosis. Finally, as the long-lived Fas protein remained stable during the early period of infection, experiments
with the HSV-1 UL39 deletion mutant ICP6∆ showed that HSV-1 R1 could be essential for the protection of HSV-1-infected cells against FasL. 相似文献
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998.
Arnaud Foulquier Florian Mermillod-Blondin Bernard Montuelle Sylvain Dolédec Bernadette Volat Janine Gibert 《Ecosystems》2011,14(8):1339-1353
Groundwaters are increasingly viewed as resource-limited ecosystems in which fluxes of dissolved organic carbon (DOC) from
surface water are efficiently mineralized by a consortium of microorganisms which are grazed by invertebrates. We tested for
the effect of groundwater recharge on resource supply and trophic interactions by measuring physico-chemistry, microbial activity
and biomass, structure of bacterial communities and invertebrate density at three sites intensively recharged with surface
water. Comparison of measurements made in recharge and control well clusters at each site showed that groundwater recharge
significantly increased fluxes of DOC and phosphate, elevated groundwater temperature, and diminished dissolved oxygen (DO).
Microbial biomass and activity were significantly higher in recharge well clusters but stimulation of autochthonous microorganisms
was not associated with a major shift in bacterial community structure. Invertebrate assemblages were not significantly more
abundant in recharge well clusters and did not show any relationship with microbial biomass and activity. Microbial communities
were bottom-up regulated by DOC and nutrient fluxes but trophic interactions between microorganisms and invertebrates were
apparently limited by environmental stresses, particularly DO depletion and groundwater warming. Hydrological connectivity
is a key factor regulating the function of DOC-based groundwater food webs as it influences both resource availability for
microorganisms and environmental stresses which affect energy transfer to invertebrates and top-down control on microorganisms. 相似文献
999.
Laure-Emmanuelle Zaragosi Brigitte Wdziekonski Kevin Le Brigand Phi Villageois Bernard Mari Rainer Waldmann Christian Dani Pascal Barbry 《Genome biology》2011,12(7):R64
Background
In severe obesity, as well as in normal development, the growth of adipose tissue is the result of an increase in adipocyte size and numbers, which is underlain by the stimulation of adipogenic differentiation of precursor cells. A better knowledge of the pathways that regulate adipogenesis is therefore essential for an improved understanding of adipose tissue expansion. As microRNAs (miRNAs) have a critical role in many differentiation processes, our study aimed to identify the role of miRNA-mediated gene silencing in the regulation of adipogenic differentiation. 相似文献1000.
Wine flavor and aroma 总被引:1,自引:0,他引:1
The perception of wine flavor and aroma is the result of a multitude of interactions between a large number of chemical compounds
and sensory receptors. Compounds interact and combine and show synergistic (i.e., the presence of one compound enhances the
perception of another) and antagonistic (a compound suppresses the perception of another) interactions. The chemical profile
of a wine is derived from the grape, the fermentation microflora (in particular the yeast Saccharomyces cerevisiae), secondary microbial fermentations that may occur, and the aging and storage conditions. Grape composition depends on the
varietal and clonal genotype of the vine and on the interaction of the genotype and its phenotype with many environmental
factors which, in wine terms, are usually grouped under the concept of “terroir” (macro, meso and microclimate, soil, topography).
The microflora, and in particular the yeast responsible for fermentation, contributes to wine aroma by several mechanisms:
firstly by utilizing grape juice constituents and biotransforming them into aroma- or flavor-impacting components, secondly
by producing enzymes that transform neutral grape compounds into flavor-active compounds, and lastly by the de novo synthesis
of many flavor-active primary (e.g., ethanol, glycerol, acetic acid, and acetaldehyde) and secondary metabolites (e.g., esters,
higher alcohols, fatty acids). This review aims to present an overview of the formation of wine flavor and aroma-active components,
including the varietal precursor molecules present in grapes and the chemical compounds produced during alcoholic fermentation
by yeast, including compounds directly related to ethanol production or secondary metabolites. The contribution of malolactic
fermentation, ageing, and maturation on the aroma and flavor of wine is also discussed. 相似文献