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361.
362.
The solubilization and reconstitution of bone collagen 总被引:1,自引:0,他引:1
363.
364.
Multiple growth- and differentiation-inducing polypeptide factors bind to and activate transmembrane receptors tyrosine kinases (RTKs), to instigate a plethora of biochemical cascades culminating in regulation of cell fate. We concentrate on the four linear mitogen-activated protein kinase (MAPK) cascades, and highlight organizational and functional features relevant to their action downstream to RTKs. Two cellular outcomes of growth factor action, namely proliferation and migration, are critically regulated by MAPKs and we detail the underlying molecular mechanisms. Hyperactivation of MAPKs, primarily the Erk pathway, is a landmark of cancer. We describe the many links of MAPKs to tumor biology and review studies that identified machineries permitting prolongation of MAPK signaling. Models attributing signal integration to both phosphorylation of MAPK substrates and to MAPK-regulated gene expression may shed light on the remarkably diversified functions of MAPKs acting downstream to activated RTKs. 相似文献
365.
C. J. Cao R. J. Mioduszewski D. E. Menking J. J. Valdes E. J. Katz M. E. Eldefrawi A. T. Eldefrawi 《In vitro cellular & developmental biology. Animal》1999,35(9):493-500
Summary Organophosphate (OP) anticholinesterases were found to modulate metabolic activities of human neuroblastoma cells and hepatocytes,
which was detectable by the Cytosensor? microphysiometer. The nerve gas ethyl-S-2-diisopropylaminoethyl methylphosphorothiolate (VX), at 10 μM, produced significant reduction in cell metabolism within 2 min, as measured by changes in the acidification rate of the
medium. The reduction was dose-and time-dependent and irreversible after 4 h of exposure. Two alkaline degradation products
of VX produced no cytotoxicity. Exposure for 24 h to 3 μM VX caused 36% and 94% irreversible loss of metabolism in hepatocytes and neuroblastoma cells, respectively. The insecticides
parathion and chlorpyrifos stimulated hepatocyte metabolism but inhibited neuroblastoma cells. Their oxons were more active.
Exposure of neuroblastoma cells for 4 h to VX, parathion, paraoxon, diisopropylfluorophosphate or chlorpyrifos gave an LC50 of 65, 775, 640, 340, or 672 μM, respectively, whereas 24 h gave an LC50 of 0.7, 3.7, 2.5, 29, and 31 μM, respectively. Preincubation of hepatocytes with phenobarbital enhanced their response to parathion and VX due to metabolic
bioactivation. Atropine partially blocked the effects of VX and paraoxon on both cell types, which suggests the involvement
of a muscarinic receptor as the target for cytotoxicity. There was no correlation between OP in vivo neurotoxicity and in
vitro cytotoxicity. It is suggested that the former results from their cholinesterase inhibition, while the latter results
from action on different targets and requires much higher concentrations. 相似文献
366.
Isotopic evidence for futile cycles in liver cells 总被引:11,自引:0,他引:11
D G Clark R Rognstad J Katz 《Biochemical and biophysical research communications》1973,54(3):1141-1148
To estimate futile cycles in the metabolism of glucose in liver, rat hepatocytes were incubated with glucose labelled with tritium in position 2 and 5 and uniformly with 14C. The yield in water from 2-3H glucose was 1.5 times that from 5-3H glucose and 2 to 3 times that of 14C utilization. Lactate addition had little effect on the water yield from 2-3H glucose but depressed that from 5-3H glucose and utilization of 14C. Our results indicate the occurrence of futile cycles glucose → glucose-6P → glucose and fructose-6P → fructose 1,6diP → fructose-6P in rat liver. An estimate of recycling at the glucose-6P level is presented. 相似文献
367.
Photosynthetic inorganic carbon utilization and growth of Porphyra linearis (Rhodophyta) 总被引:2,自引:0,他引:2
Alvaro Israel Shlomit Katz Zvy Dubinsky John E. Merrill Michael Friedlander 《Journal of applied phycology》1999,11(5):447-453
Photosynthetic (oxygen evolution) and growth (biomass increase) responses to ambient pH and inorganic carbon (Ci) supply were
determined for Porphyralinearis grown in 0.5 L glass cylinders in the laboratory, or in 40 L fibreglass outdoor tanks with running seawater. While net photosynthetic
rates were uniform at pH 6.0–8.0, dropping only at pH 8.7, growth rates were significantly affected by pH levels other than
that of seawater (c. pH 8.3). In glass cylinders, weekly growth rates averaged 76% at external pH 8.0, 13% at pH 8.7 and 26%
at pH 7.0. Photosynthetic O2 evolution on a daily basis(i.e. total O2 evolved during day time less total O2 consumed during night time) was similar to the growth responses at all experimental pH levels, apparently due to high dark
respiration rates measured at acidic pH. Weekly growth rates averaged 53% in algae grown in fibreglass tanks aerated with
regular air (360 mg L-1 CO2) and 28% in algae grown in tanks aerated with CO2-enriched air (750 mg L-1 CO2). The pH of the seawater medium in which P. linear is was grown increased slightly during the day and only rarely reached 9.0. The pH at the boundary layer of algae submerged
in seawater increased in response to light reaching, about pH 8.9 within minutes, or remained unchanged for algae submerged
in a CO2-free artificial sea water medium. Photosynthesis of P. linearissaturated at Ci concentrations of seawater (K0.5560 μM at pH 8.2) and showed low photosynthetic affinity for CO2(K0.5 61 μM) at pH 6.0. It is therefore concluded that P. linearisuses primarily CO2 with HCO3
- being an alternative source of Ci for photosynthesis. Its fast growth could be related to the enzyme carbonic anhydrase whose
activity was detected intra- and extracellularly.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
368.
A Mouse Model for the Evaluation of Pathogenesis and Immunity to Influenza A (H5N1) Viruses Isolated from Humans 总被引:17,自引:0,他引:17
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Xiuhua Lu Terrence M. Tumpey Timothy Morken Sherif R. Zaki Nancy J. Cox Jacqueline M. Katz 《Journal of virology》1999,73(7):5903-5911
During 1997 in Hong Kong, 18 human cases of respiratory illness, including 6 fatalities, were caused by highly pathogenic avian influenza A (H5N1) viruses. Since H5 viruses had previously been isolated only from avian species, the outbreak raised questions about the ability of these viruses to cause severe disease and death in humans. To better understand the pathogenesis and immunity to these viruses, we have used the BALB/c mouse model. Four H5N1 viruses replicated equally well in the lungs of mice without prior adaptation but differed in lethality for mice. H5N1 viruses that were highly lethal for mice were detected in multiple organs, including the brain. This is the first demonstration of an influenza A virus that replicates systemically in a mammalian species and is neurotropic without prior adaptation. The mouse model was also used to evaluate a strategy of vaccination against the highly pathogenic avian H5N1 viruses, using an inactivated vaccine prepared from nonpathogenic A/Duck/Singapore-Q/F119-3/97 (H5N3) virus that was antigenically related to the human H5N1 viruses. Mice administered vaccine intramuscularly, with or without alum, were completely protected from lethal challenge with H5N1 virus. Protection from infection was also observed in 70% of animals administered vaccine alone and 100% of mice administered vaccine with alum. The protective effect of vaccination correlated with the level of virus-specific serum antibody. These results suggests a strategy of vaccine preparedness for rapid intervention in future influenza pandemics that uses antigenically related nonpathogenic viruses as vaccine candidates. 相似文献
369.
Andrew M. Haidle Kaleen K. Childers Anna A. Zabierek Jason D. Katz James P. Jewell Yongquan Hou Michael D. Altman Alexander Szewczak Dapeng Chen Andreas Harsch Mansuo Hayashi Lee Warren Michael Hutton Hugh Nuthall Matt G. Stanton Ian W. Davies Ben Munoz Alan Northrup 《Bioorganic & medicinal chemistry letters》2017,27(1):109-113
Attempts to optimize pharmacokinetic properties in a promising series of pyrrolopyrimidinone MARK inhibitors for the treatment of Alzheimer’s disease are described. A focus on physical properties and ligand efficiency while prosecuting this series afforded key tool compounds that revealed a large discrepancy in the rat in vitro–in vivo DMPK (Drug Metabolism/Pharmacokinetics) correlation. These differences prompted an in vivo rat disposition study employing a radiolabeled representative of the series, and the results from this experiment justified the termination of any further optimization efforts. 相似文献
370.
Structural insights into human microsomal epoxide hydrolase by combined homology modeling,molecular dynamics simulations,and molecular docking calculations
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Patricia Saenz‐Méndez Aline Katz María Lucía Pérez‐Kempner Oscar N. Ventura Marta Vázquez 《Proteins》2017,85(4):720-730
A new homology model of human microsomal epoxide hydrolase was derived based on multiple templates. The model obtained was fully evaluated, including MD simulations and ensemble‐based docking, showing that the quality of the structure is better than that of only previously known model. Particularly, a catalytic triad was clearly identified, in agreement with the experimental information available. Analysis of intermediates in the enzymatic mechanism led to the identification of key residues for substrate binding, stereoselectivity, and intermediate stabilization during the reaction. In particular, we have confirmed the role of the oxyanion hole and the conserved motif (HGXP) in epoxide hydrolases, in excellent agreement with known experimental and computational data on similar systems. The model obtained is the first one that fully agrees with all the experimental observations on the system. Proteins 2017; 85:720–730. © 2016 Wiley Periodicals, Inc. 相似文献