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991.
Lyme disease risk is increasing in the United States due in part to the spread of blacklegged ticks Ixodes
scapularis, the principal vector of the spirochetal pathogen Borrelia
burgdorferi. A 5-year study was undertaken to investigate hypothesized coinvasion of I. scapularis and B. burgdorferi in Lower Michigan. We tracked the spatial and temporal dynamics of the tick and spirochete using mammal, bird, and vegetation
drag sampling at eight field sites along coastal and inland transects originating in a zone of recent I.
scapularis establishment. We document northward invasion of these ticks along Michigan’s west coast during the study period; this pattern
was most evident in ticks removed from rodents. B.
burgdorferi infection prevalences in I.
scapularis sampled from vegetation in the invasion zone were 9.3% and 36.6% in nymphs and adults, respectively, with the majority of
infection (95.1%) found at the most endemic site. There was no evidence of I. scapularis invasion along the inland transect; however, low-prevalence B.
burgdorferi infection was detected in other tick species and in wildlife at inland sites, and at northern coastal sites in years before
the arrival of I.
scapularis. These infections suggest that cryptic B.
burgdorferi transmission by other vector-competent tick species is occurring in the absence of I.
scapularis. Other Borrelia spirochetes, including those that group with B. miyamotoi and B. andersonii, were present at a low prevalence within invading ticks and local wildlife. Reports of Lyme disease have increased significantly
in the invasion zone in recent years. This rapid blacklegged tick invasion—measurable within 5 years—in combination with cryptic
pathogen maintenance suggests a complex ecology of Lyme disease emergence in which wildlife sentinels can provide an early
warning of disease emergence. 相似文献
992.
993.
Two models have been proposed for endophilin function in synaptic vesicle (SV) endocytosis. The scaffolding model proposes that endophilin's SH3 domain recruits essential endocytic proteins, whereas the membrane-bending model proposes that the BAR domain induces positively curved membranes. We show that mutations disrupting the scaffolding function do not impair endocytosis, whereas those disrupting membrane bending cause significant defects. By anchoring endophilin to the plasma membrane, we show that endophilin acts prior to scission to promote endocytosis. Despite acting at the plasma membrane, the majority of endophilin is targeted to the SV pool. Photoactivation studies suggest that the soluble pool of endophilin at synapses is provided by unbinding from the adjacent SV pool and that the unbinding rate is regulated by exocytosis. Thus, endophilin participates in an association-dissociation cycle with SVs that parallels the cycle of exo- and endocytosis. This endophilin cycle may provide a mechanism for functionally coupling endocytosis and exocytosis. 相似文献
994.
Mariusz Lamentowicz Łukasz Lamentowicz Willem O. van der Knaap Maciej Gąbka Edward A. D. Mitchell 《Microbial ecology》2010,59(3):499-510
We studied the vegetation, testate amoebae and abiotic variables (depth of the water table, pH, electrical conductivity, Ca
and Mg concentrations of water extracted from mosses) along the bog to extremely rich fen gradient in sub-alpine peatlands
of the Upper Engadine (Swiss Alps). Testate amoeba diversity was correlated to that of mosses but not of vascular plants.
Diversity peaked in rich fen for testate amoebae and in extremely rich fen for mosses, while for testate amoebae and mosses
it was lowest in bog but for vascular plants in extremely rich fen. Multiple factor and redundancy analyses (RDA) revealed
a stronger correlation of testate amoebae than of vegetation to water table and hydrochemical variables and relatively strong
correlation between testate amoeba and moss community data. In RDA, hydrochemical variables explained a higher proportion
of the testate amoeba and moss data than water table depth. Abiotic variables explained a higher percentage of the species
data for testate amoebae (30.3% or 19.5% for binary data) than for mosses (13.4%) and vascular plants (10%). These results
show that (1) vascular plant, moss and testate amoeba communities respond differently to ecological gradients in peatlands
and (2) testate amoebae are more strongly related than vascular plants to the abiotic factors at the mire surface. These differences
are related to vertical trophic gradients and associated niche differentiation. 相似文献
995.
Leonid V. Kurepin Linda J. Walton Edward C. Yeung C. C. Chinnappa David M. Reid 《Plant Growth Regulation》2010,62(1):43-50
Shade light found in ecological niches where plants are growing under a canopy or in proximity of taller neighbouring vegetation consist mainly of two separate light signals: low red to far-red ratio and low photosynthetically active radiation (PAR). The effect of the latter on the growth of 7-day old sunflower shoots was examined by assessing hypocotyl, cotyledon and leaf tissue growth under three varying PAR levels: near-normal of 1,000 μmol m?2 s?1, low of 100 μmol m?2 s?1 and very low of 10 μmol m?2 s?1. Then, the possible interaction between PAR signaling and ethylene in regulating growth of these sunflower tissues was investigated. The results showed that gradual decrease in PAR level increases hypocotyl elongation and decreases ethylene evolution. However, gradual decrease in PAR level decreases cotyledon and leaf growth and increases ethylene evolution. Thus it seems possible that PAR regulation of shoot growth is mediated by changes in ethylene evolution in tissue specific manner. This hypothesis was supported by experiments with the ethylene releasing factor, ethephon, and the ethylene biosynthesis inhibitor, AVG, as well as by transfer experiments where sunflower seedlings were transferred from one PAR regime to another with subsequent growth and ethylene measurements. 相似文献
996.
Shohei Shinozaki Yoko Inoue Makiko Fukaya Edward A. Carter Young Ming-Yu Alan Fischman Ronald Tompkins Masao Kaneki 《Biochemical and biophysical research communications》2010,391(3):1459-710
Endotoxemia plays an important role in the pathogenesis of sepsis and is accompanied by dysregulated apoptosis of immune and non-immune cells. Treatment with statins reduces mortality in rodent models of sepsis and endotoxemia. Inhibition of protein isoprenylation, including farnesylation, has been proposed as a mechanism to mediate the lipid-lowering-independent effects of statins. Nonetheless, the effects of the inhibition of isoprenylation have not yet been studied. To investigate the role of farnesylation, we evaluated the effects of farnesyltransferase inhibitor and statin on survival following lipopolysaccharide (LPS) challenge in mice. Both simvastatin (2 mg/kg BW) and FTI-277 (20 mg/kg BW) treatment improved survival by twofold after LPS injection, as compared with vehicle alone (p < 0.01). LPS-induced cleavage (activation) of caspase-3, an indicator of apoptotic change, and increased protein expression of proapoptotic molecules, Bax and Bim, and activation of c-Jun NH2-terminal kinase (JNK/SAPK) in the liver and spleen were attenuated by both simvastatin and FTI-277. These results demonstrate that farnesyltransferase inhibitor as well as statin significantly reduced LPS-induced mortality in mice. Our findings also suggest that inhibition of protein farnesylation may contribute to the lipid-lowering-independent protective effects of statins in endotoxemia, and that protein farnesylation may play a role in LPS-induced stress response, including JNK/SAPK activation, and apoptotic change. Our data argue that farnesyltransferase may be a potential molecular target for treating patients with endotoxemia. 相似文献
997.
Mohd Akif Edward D. Sturrock Brian O. Bachmann 《Biochemical and biophysical research communications》2010,398(3):532-5980
Angiotensin-I converting enzyme (ACE, a zinc dependent dipeptidyl carboxypeptidase) is a major target of drugs due to its role in the modulation of blood pressure and cardiovascular disorders. Here we present a crystal structure of AnCE (an ACE homologue from Drosophila melanogaster with a single enzymatic domain) in complex with a natural product-phosphonotripeptide, K-26 at 1.96 Å resolution. The inhibitor binds exclusively in the S1 and S2 binding pockets of AnCE (coordinating the zinc ion) through ionic and hydrogen bond interactions. A detailed structural comparison of AnCE·K-26 complex with individual domains of human somatic ACE provides useful information for further exploration of ACE inhibitor pharmacophores involving phosphonic acids. 相似文献
998.
There is still not an appealing and testable model to explain how single-celled organisms, usually following fusion of male
and female gametes, proceed to grow and evolve into multi-cellular, complexly differentiated systems, a particular species
following virtually an invariant and unique growth pattern. An intrinsic electrical oscillator, resembling the cardiac pacemaker,
may explain the process. Highly auto-correlated, it could live independently of ordinary thermodynamic processes which mandate
increasing disorder, and could coordinate growth and differentiation of organ anlage. 相似文献
999.
Willem Kuyken Sarah Byford Richard Byng Tim Dalgleish Glyn Lewis Rod Taylor Edward R Watkins Rachel Hayes Paul Lanham David Kessler Nicola Morant Alison Evans 《Trials》2010,11(1):1-10
Background
The total effect of a medication is the sum of its drug effect, placebo effect (meaning response), and their possible interaction. Current interpretation of clinical trials' results assumes no interaction. Demonstrating such an interaction has been difficult due to lack of an appropriate study design.Methods
180 adults were randomized to caffeine (300 mg) or placebo groups. Each group received the assigned intervention described by the investigators as caffeine or placebo, in a randomized crossover design. 4-hour-area-under-the-curve of energy, sleepiness, nausea (on 100 mm visual analog scales), and systolic blood pressure levels as well as caffeine pharmacokinetics (in 22 volunteers nested in the caffeine group) were determined. Caffeine drug, placebo, placebo-plus-interaction, and total effects were estimated by comparing outcomes after, receiving caffeine described as placebo to receiving placebo described as placebo, receiving placebo described as caffeine or placebo, receiving caffeine described as caffeine or placebo, and receiving caffeine described as caffeine to receiving placebo described as placebo, respectively.Results
The placebo effect on area-under-the-curve of energy (mean difference) and sleepiness (geometric mean ratio) was larger than placebo-plus-interaction effect (16.6 [95% CI, 4.1 to 29.0] vs. 8.4 [-4.2 to 21.0] mm*hr and 0.58 [0.39 to 0.86] vs. 0.69 [0.49 to 0.97], respectively), similar in size to drug effect (20.8 [3.8 to 37.8] mm*hr and 0.49 [0.30 to 0.91], respectively), and its combination with the later was larger than total caffeine effect (29.5 [11.9 to 47.1] mm*hr and 0.37 [0.22 to 0.64]). Placebo-plus-interaction effect increased caffeine terminal half-life by 0.40 [0.12 to 0.68] hr (P = 0.007).Conclusions
Drug and placebo effects of a medication may be less than additive, which influences the interpretation of clinical trials. The placebo effect may increase active drug terminal half-life, a novel mechanism of placebo action.Trial Registration
ClinicalTrials.gov identification number - NCT00426010. 相似文献1000.
Megan H. Wright William P. Heal David J. Mann Edward W. Tate 《Journal of chemical biology》2010,3(1):19-35
N-myristoylation is the attachment of a 14-carbon fatty acid, myristate, onto the N-terminal glycine residue of target proteins,
catalysed by N-myristoyltransferase (NMT), a ubiquitous and essential enzyme in eukaryotes. Many of the target proteins of NMT are crucial
components of signalling pathways, and myristoylation typically promotes membrane binding that is essential for proper protein
localisation or biological function. NMT is a validated therapeutic target in opportunistic infections of humans by fungi
or parasitic protozoa. Additionally, NMT is implicated in carcinogenesis, particularly colon cancer, where there is evidence
for its upregulation in the early stages of tumour formation. However, the study of myristoylation in all organisms has until
recently been hindered by a lack of techniques for detection and identification of myristoylated proteins. Here we introduce
the chemistry and biology of N-myristoylation and NMT, and discuss new developments in chemical proteomic technologies that are meeting the challenge of
studying this important co-translational modification in living systems. 相似文献