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61.
62.
Wolfs JL Comfurius P Bekers O Zwaal RF Balasubramanian K Schroit AJ Lindhout T Bevers EM 《Cellular and molecular life sciences : CMLS》2009,66(2):314-323
The exposure of phosphatidylserine (PS) at the cell surface plays a critical role in blood coagulation and serves as a macrophage
recognition moiety for the engulfment of apoptotic cells. Previous observations have shown that a high extracellular [K+] and selective K+ channel blockers inhibit PS exposure in platelets and erythrocytes. Here we show that the rate of PS exposure in erythrocytes
decreases by ~50% when the intracellular [K+] increases from 0 to physiological concentrations. Using resealed erythrocyte membranes, we further show that lipid scrambling
is inducible by raising the intracellular [Ca2+] and that K+ ions have a direct inhibitory effect on this process. Lipid scrambling in resealed ghosts occurs in the absence of cell shrinkage
and microvesicle formation, processes that are generally attributed to Ca2+-induced lipid scrambling in intact erythrocytes. Thus, opening of Ca2+-sensitive K+ channels causes loss of intracellular K+ that results in reduced intrinsic inhibitory effect of these ions on scramblase activity.
Received 11 September 2008; received after revision 17 October 2008; accepted 27 October 2008 相似文献
63.
Celso O. Azevedo Simon van Noort David G. Notton 《Journal of Natural History》2018,52(23-24):1537-1549
Holepyris semiruber Kieffer is redescribed and illustrated based on freshly collected specimens. Holepyris semiruber var. striatipleura Kieffer is considered a colour variant of this species and therefore a junior synonym of H. semiruber syn. nov. This species is transferred to Disepyris, D. semiruber (Kieffer) comb. nov., based on the possession of a short 2r-rs&Rs vein in the fore wing and presence of long flat spine-shaped setae on the outer (posterior) surface of the protarsi. The male is described for the first time from new specimens collected in South Africa. This species is recorded for the first time from Namibia and Zimbabwe. All photographs are available on www.waspweb.org. 相似文献
64.
65.
Valdar W Solberg LC Gauguier D Burnett S Klenerman P Cookson WO Taylor MS Rawlins JN Mott R Flint J 《Nature genetics》2006,38(8):879-887
Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits. 相似文献
66.
Gilbert SL Zhang L Forster ML Anderson JR Iwase T Soliven B Donahue LR Sweet HO Bronson RT Davisson MT Wollmann RL Lahn BT 《Nature genetics》2006,38(2):245-250
Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases. 相似文献
67.
Lubelski J Rink R Khusainov R Moll GN Kuipers OP 《Cellular and molecular life sciences : CMLS》2008,65(3):455-476
This review discusses the state-of-the-art in molecular research on the most prominent and widely applied lantibiotic, i.e., nisin. The developments in understanding its complex biosynthesis and mode of action are highlighted. Moreover, novel applications
arising from engineering either nisin itself, or from the construction of totally novel dehydrated and/or lanthionine-containing
peptides with desired bioactivities are described. Several challenges still exist in understanding the immunity system and
the unique multiple reactions occurring on a single substrate molecule, carried out by the dehydratase NisB and the cyclization
enzyme NisC. The recent elucidation of the 3-D structure of NisC forms the exciting beginning of further 3-D-structure determinations
of the other biosynthetic enzymes, transporters and immunity proteins. Advances in achieving in vitro activities of lanthionine-forming enzymes will greatly enhance our understanding of the molecular characteristics of the
biosynthesis process, opening up new avenues for developing unique and novel biocatalytic processes.
Received 9 April 2007; received after revision 31 August 2007; accepted 28 September 2007 相似文献
68.
Cohausz O Blenn C Malanga M Althaus FR 《Cellular and molecular life sciences : CMLS》2008,65(4):644-655
Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor
(AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and triggers cell death. In living cells, PAR
molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we
determined the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG),
the key enzymes configuring PAR molecules, in cell death induced by an alkylating agent. We found that PARP-1, but not PARP-2
and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1. PARP-1 seems
to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved.
Received 7 November 2007; received after revision 19 December 2007; accepted 21 December 2007
O. Cohausz, C. Blenn: These two authors contributed equally to this work. 相似文献
69.
Shin JM Vagin O Munson K Kidd M Modlin IM Sachs G 《Cellular and molecular life sciences : CMLS》2008,65(2):264-281
Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration;
therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor
were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell
hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are
the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities.
Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of
a novel class of agents, the acid pump antagonists.
Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007 相似文献
70.