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991.
Haning H Mueller U Schmidt G Schmeck C Voehringer V Kretschmer A Bischoff H 《Bioorganic & medicinal chemistry letters》2007,17(14):3992-3996
Novel heterocyclic thyromimetics are presented carrying carboxy-substituted benzofurans or sulfur containing heterocycles, as replacements for the amino acid side chain of T3. Potent agonists were identified in both series. SAR trends are examined and found to be mostly consistent with previously published thyromimetics. The lack of isoform selectivity demonstrated with isoform-selective transient THR transfection assays has been confirmed by corresponding in vivo studies. 相似文献
992.
Peripheral nerve demyelination caused by a mutant Rho GTPase guanine nucleotide exchange factor, frabin/FGD4 总被引:2,自引:1,他引:1 下载免费PDF全文
Stendel C Roos A Deconinck T Pereira J Castagner F Niemann A Kirschner J Korinthenberg R Ketelsen UP Battaloglu E Parman Y Nicholson G Ouvrier R Seeger J De Jonghe P Weis J Krüttgen A Rudnik-Schöneborn S Bergmann C Suter U Zerres K Timmerman V Relvas JB Senderek J 《American journal of human genetics》2007,81(1):158-164
GTPases of the Rho subfamily are widely involved in the myelination of the vertebrate nervous system. Rho GTPase activity is temporally and spatially regulated by a set of specific guanine nucleotide exchange factors (GEFs). Here, we report that disruption of frabin/FGD4, a GEF for the Rho GTPase cell-division cycle 42 (Cdc42), causes peripheral nerve demyelination in patients with autosomal recessive Charcot-Marie-Tooth (CMT) neuropathy. These data, together with the ability of frabin to induce Cdc42-mediated cell-shape changes in transfected Schwann cells, suggest that Rho GTPase signaling is essential for proper myelination of the peripheral nervous system. 相似文献
993.
Schneiker S Perlova O Kaiser O Gerth K Alici A Altmeyer MO Bartels D Bekel T Beyer S Bode E Bode HB Bolten CJ Choudhuri JV Doss S Elnakady YA Frank B Gaigalat L Goesmann A Groeger C Gross F Jelsbak L Jelsbak L Kalinowski J Kegler C Knauber T Konietzny S Kopp M Krause L Krug D Linke B Mahmud T Martinez-Arias R McHardy AC Merai M Meyer F Mormann S Muñoz-Dorado J Perez J Pradella S Rachid S Raddatz G Rosenau F Rückert C Sasse F Scharfe M Schuster SC Suen G Treuner-Lange A Velicer GJ Vorhölter FJ 《Nature biotechnology》2007,25(11):1281-1289
The genus Sorangium synthesizes approximately half of the secondary metabolites isolated from myxobacteria, including the anti-cancer metabolite epothilone. We report the complete genome sequence of the model Sorangium strain S. cellulosum So ce56, which produces several natural products and has morphological and physiological properties typical of the genus. The circular genome, comprising 13,033,779 base pairs, is the largest bacterial genome sequenced to date. No global synteny with the genome of Myxococcus xanthus is apparent, revealing an unanticipated level of divergence between these myxobacteria. A large percentage of the genome is devoted to regulation, particularly post-translational phosphorylation, which probably supports the strain's complex, social lifestyle. This regulatory network includes the highest number of eukaryotic protein kinase-like kinases discovered in any organism. Seventeen secondary metabolite loci are encoded in the genome, as well as many enzymes with potential utility in industry. 相似文献
994.
Polyglutamylases are enzymes that form polyglutamate side chains of variable lengths on proteins. Polyglutamylation of tubulin is believed to regulate interactions of microtubules (MTs) with MT-associated proteins and molecular motors. Subpopulations of MTs are differentially polyglutamylated, yet only one modifying enzyme has been discovered in mammals. In an attempt to better understand the heterogeneous appearance of tubulin polyglutamylation, we searched for additional enzymes and report here the identification of six mammalian polyglutamylases. Each of them has a characteristic mode of catalysis and generates distinct patterns of modification on MTs, which can be further diversified by cooperation of multiple enzymes. Polyglutamylases are restricted to confined tissues and subtypes of MTs by differential expression and localization. In conclusion, we propose a multienzyme mechanism of polyglutamylation that can explain how the diversity of polyglutamylation on selected types of MTs is controlled at the molecular level. 相似文献
995.
996.
Zheng Lei Evlyukhin Andrey Overmeyer Ludger Reinhardt Carsten 《Plasmonics (Norwell, Mass.)》2019,14(6):1547-1554
Plasmonics - 3D metallic structures with symmetrically curved surfaces are proposed for surface plasmon polaritons (SPPs) deflection and concentration. Two-photon polymerization (2PP) and a... 相似文献
997.
998.
Inhibitory motor control is a core function of cognitive control. Evidence from diverse experimental approaches has linked this function to a mostly right-lateralized network of cortical and subcortical areas, wherein a signal from the frontal cortex to the basal ganglia is believed to trigger motor-response cancellation. Recently, however, it has been recognized that in the context of typical motor-control paradigms those processes related to actual response inhibition and those related to the attentional processing of the relevant stimuli are highly interrelated and thus difficult to distinguish. Here, we used fMRI and a modified Stop-signal task to specifically examine the role of perceptual and attentional processes triggered by the different stimuli in such tasks, thus seeking to further distinguish other cognitive processes that may precede or otherwise accompany the implementation of response inhibition. In order to establish which brain areas respond to sensory stimulation differences by rare Stop-stimuli, as well as to the associated attentional capture that these may trigger irrespective of their task-relevance, we compared brain activity evoked by Stop-trials to that evoked by Go-trials in task blocks where Stop-stimuli were to be ignored. In addition, region-of-interest analyses comparing the responses to these task-irrelevant Stop-trials, with those to typical relevant Stop-trials, identified separable activity profiles as a function of the task-relevance of the Stop-signal. While occipital areas were mostly blind to the task-relevance of Stop-stimuli, activity in temporo-parietal areas dissociated between task-irrelevant and task-relevant ones. Activity profiles in frontal areas, in turn, were activated mainly by task-relevant Stop-trials, presumably reflecting a combination of triggered top-down attentional influences and inhibitory motor-control processes. 相似文献
999.
Kervinen J Ma H Bayoumy S Schubert C Milligan C Lewandowski F Moriarty K Desjarlais RL Ramachandren K Wang H Harris CA Grasberger B Todd M Springer BA Deckman I 《Archives of biochemistry and biophysics》2006,449(1-2):47-56
MAPK-activated protein kinase-2 (MAPKAPK2) regulates the synthesis of tumor necrosis factor and other cytokines and is a potential drug target for inflammatory diseases. Five protein constructs were produced in 4-10mg quantities per liter of culture media using baculovirus-infected insect cells and characterized for kinase activity, thermal stability, and ligand-binding affinity. Compared to construct 1-370, removal of the C-terminal autoinhibitory peptide in 1-338 resulted in a destabilized but partially active nonphosphorylated enzyme; phosphorylation of 1-338 by p38alpha further increased activity 12-fold. A putative constitutively active mutant, 1-370/T222E/T334E, was 6.3-fold less active than phosphorylated 1-370. ThermoFluor, an equilibrium ligand-binding assay, was used to measure nucleotide analogue affinity for various constructs. Binding of phosphorylated nucleotides was Mg(2+)-dependent. Residues 1-40 were required for high-affinity binding of ADP, ATPgammaS, staurosporine, and K252a. A mutation M138A rendered 1-370 susceptible to p38-inhibitors SB-203580 and SB-202190 with IC50 values of 17.4 and 14.1 microM, respectively. Taken together, these studies provide information on the mechanism of ligand-binding to MAPKAPK2 that can be used in the search for selective small-molecule inhibitors. 相似文献
1000.
Stephan Waack Oliver Keller Roman Asper Thomas Brodag Carsten Damm Wolfgang Florian Fricke Katharina Surovcik Peter Meinicke Rainer Merkl 《BMC bioinformatics》2006,7(1):142-12