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171.
All living organisms use ion channels to regulate the transport of ions across cellular membranes. Certain ion channels are classed as voltage-dependent because they have a voltage-sensing structure that induces their pores to open in response to changes in the cell membrane voltage. Until recently, the voltage-dependent K+, Ca2+ and Na+ channels were regarded as a unique development of eukaryotic cells, adapted to accomplish specialized electrical signalling, as exemplified in neurons. Here we present the functional characterization of a voltage-dependent K+ (K(V)) channel from a hyperthermophilic archaebacterium from an oceanic thermal vent. This channel possesses all the functional attributes of classical neuronal K(V) channels. The conservation of function reflects structural conservation in the voltage sensor as revealed by specific, high-affinity interactions with tarantula venom toxins, which evolved to inhibit eukaryotic K(V) channels. 相似文献
172.
Glycine binding primes NMDA receptor internalization 总被引:18,自引:0,他引:18
NMDA (N-methyl-d-aspartate) receptors (NMDARs) are a principal subtype of excitatory ligand-gated ion channel with prominent roles in physiological and disease processes in the central nervous system. Recognition that glycine potentiates NMDAR-mediated currents as well as being a requisite co-agonist of the NMDAR subtype of 'glutamate' receptor profoundly changed our understanding of chemical synaptic communication in the central nervous system. The binding of both glycine and glutamate is necessary to cause opening of the NMDAR conductance pore. Although binding of either agonist alone is insufficient to cause current flow through the channel, we report here that stimulation of the glycine site initiates signalling through the NMDAR complex, priming the receptors for clathrin-dependent endocytosis. Glycine binding alone does not cause the receptor to be endocytosed; this requires both glycine and glutamate site activation of NMDARs. The priming effect of glycine is mimicked by the NMDAR glycine site agonist d-serine, and is blocked by competitive glycine site antagonists. Synaptic as well as extrasynaptic NMDARs are primed for internalization by glycine site stimulation. Our results demonstrate transmembrane signal transduction through activating the glycine site of NMDARs, and elucidate a model for modulating cell-cell communication in the central nervous system. 相似文献
173.
Artemisinins target the SERCA of Plasmodium falciparum 总被引:1,自引:0,他引:1
Eckstein-Ludwig U Webb RJ Van Goethem ID East JM Lee AG Kimura M O'Neill PM Bray PG Ward SA Krishna S 《Nature》2003,424(6951):957-961
Artemisinins are extracted from sweet wormwood (Artemisia annua) and are the most potent antimalarials available, rapidly killing all asexual stages of Plasmodium falciparum. Artemisinins are sesquiterpene lactones widely used to treat multidrug-resistant malaria, a disease that annually claims 1 million lives. Despite extensive clinical and laboratory experience their molecular target is not yet identified. Activated artemisinins form adducts with a variety of biological macromolecules, including haem, translationally controlled tumour protein (TCTP) and other higher-molecular-weight proteins. Here we show that artemisinins, but not quinine or chloroquine, inhibit the SERCA orthologue (PfATP6) of Plasmodium falciparum in Xenopus oocytes with similar potency to thapsigargin (another sesquiterpene lactone and highly specific SERCA inhibitor). As predicted, thapsigargin also antagonizes the parasiticidal activity of artemisinin. Desoxyartemisinin lacks an endoperoxide bridge and is ineffective both as an inhibitor of PfATP6 and as an antimalarial. Chelation of iron by desferrioxamine abrogates the antiparasitic activity of artemisinins and correspondingly attenuates inhibition of PfATP6. Imaging of parasites with BODIPY-thapsigargin labels the cytosolic compartment and is competed by artemisinin. Fluorescent artemisinin labels parasites similarly and irreversibly in an Fe2+-dependent manner. These data provide compelling evidence that artemisinins act by inhibiting PfATP6 outside the food vacuole after activation by iron. 相似文献
174.
Su HT Hsu RR Chen AB Wang YC Hsiao WS Lai WC Lee LC Sato M Fukunishi H 《Nature》2003,423(6943):974-976
Transient luminous events in the atmosphere, such as lighting-induced sprites and upwardly discharging blue jets, were discovered recently in the region between thunderclouds and the ionosphere. In the conventional picture, the main components of Earth's global electric circuit include thunderstorms, the conducting ionosphere, the downward fair-weather currents and the conducting Earth. Thunderstorms serve as one of the generators that drive current upward from cloud tops to the ionosphere, where the electric potential is hundreds of kilovolts higher than Earth's surface. It has not been clear, however, whether all the important components of the global circuit have even been identified. Here we report observations of five gigantic jets that establish a direct link between a thundercloud (altitude approximately 16 km) and the ionosphere at 90 km elevation. Extremely-low-frequency radio waves in four events were detected, while no cloud-to-ground lightning was observed to trigger these events. Our result indicates that the extremely-low-frequency waves were generated by negative cloud-to-ionosphere discharges, which would reduce the electrical potential between ionosphere and ground. Therefore, the conventional picture of the global electric circuit needs to be modified to include the contributions of gigantic jets and possibly sprites. 相似文献
175.
176.
Lappe-Siefke C Goebbels S Gravel M Nicksch E Lee J Braun PE Griffiths IR Nave KA 《Nature genetics》2003,33(3):366-374
Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss. 相似文献
177.
178.
REE geochemistry of suspended sediments from the rivers around the Yellow Sea and provenance indicators 总被引:11,自引:0,他引:11
YANGShouye LICongxian C.B.Lee T.K.Na 《科学通报(英文版)》2003,48(11):1135-1139
Rare earth element (REE) compositions of the suspended sediments from the rivers around the Yellow Sea were different in that Korean river sediments (Han, Keum and Yeongsan Rivers) yield stronger fractionations than Chinese river sediments (Changjiang, Huanghe and Yalujiang), shown by obvious enrichments of LREE (light rare earth element) relative to UCC (upper continental crust).Variations of source rock compositions in the drainage basins are responsible for the differences of REE compositions between the river sediments. REE fractionation parameters including (La/Yb)ucc and (Gd/Yb)ucc as well as the ratios of La/Sc and Th/Sc can be treated as proper proxies for identifying the Chinese river sediments from those Korean river matters, and furthermore, for studying the provenances and paleoenvironmental changes of the marginal seas of China. 相似文献
179.
Grove Mountains (GRV)99027: A new Martian meteorite 总被引:10,自引:0,他引:10
LINYangting WANGDaode MIAOBingkui OUYANGZiyuan LIUXiaohan JUYitai 《科学通报(英文版)》2003,48(16):1771-1774
We report the petrography, mineral chemistry and oxygen isotopic composition of GRV 99027, a new Martian meteorite recently collected during the 16th Chinese Antarctic Research Expedition. This meteorite consists of two textural regions. The interstitial region is characterized by the presence of plagioclase and phosphate, and higher FeO contents of olivine and orthopyroxene, in comparison with the poikilitic region. All of the observations are similar to the three known Martian lherzolites. We classify GRV 99027 as the fourth sample of Martian lherzolite. 相似文献
180.
Single-crystal gallium nitride nanotubes 总被引:22,自引:0,他引:22
Since the discovery of carbon nanotubes in 1991 (ref. 1), there have been significant research efforts to synthesize nanometre-scale tubular forms of various solids. The formation of tubular nanostructure generally requires a layered or anisotropic crystal structure. There are reports of nanotubes made from silica, alumina, silicon and metals that do not have a layered crystal structure; they are synthesized by using carbon nanotubes and porous membranes as templates, or by thin-film rolling. These nanotubes, however, are either amorphous, polycrystalline or exist only in ultrahigh vacuum. The growth of single-crystal semiconductor hollow nanotubes would be advantageous in potential nanoscale electronics, optoelectronics and biochemical-sensing applications. Here we report an 'epitaxial casting' approach for the synthesis of single-crystal GaN nanotubes with inner diameters of 30-200 nm and wall thicknesses of 5-50 nm. Hexagonal ZnO nanowires were used as templates for the epitaxial overgrowth of thin GaN layers in a chemical vapour deposition system. The ZnO nanowire templates were subsequently removed by thermal reduction and evaporation, resulting in ordered arrays of GaN nanotubes on the substrates. This templating process should be applicable to many other semiconductor systems. 相似文献