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961.
Grimm DR Colter MB Braunschweig M Alexander LJ Neame PJ Kim HK 《Cellular and molecular life sciences : CMLS》2001,58(1):148-159
Factor V is a plasma protein essential for blood coagulation. This protein is involved in activated protein C resistance,
the most common inherited thrombotic disorder known. We utilized the polymerase chain reaction to clone the porcine factor
V gene by generating overlapping clones amplified with primers chosen by comparison with known nucleotide sequences. The porcine
factor V cDNA contig encodes a predicted 2258-amino acid protein, making it the largest in comparison to the bovine, human,
and murine proteins. Porcine factor V has the highest level of homology with bovine factor V, but also has high levels of
conservation of important residues with all the species. Radiation hybrid mapping assigned the porcine factor V gene to chromosome
4. Three-dimensional models of factor V were generated and used to analyze membrane-binding sites in terms of conserved, and
therefore likely important residues.
Received 3 October 2000; revised 23 November 2000; accepted 6 December 2000 相似文献
962.
Larbalestier DC Cooley LD Rikel MO Polyanskii AA Jiang J Patnaik S Cai XY Feldmann DM Gurevich A Squitieri AA Naus MT Eom CB Hellstrom EE Cava RJ Regan KA Rogado N Hayward MA He T Slusky JS Khalifah P Inumaru K Haas M 《Nature》2001,410(6825):186-189
The discovery of superconductivity at 39 K in magnesium diboride, MgB2, raises many issues, a critical one being whether this material resembles a high-temperature copper oxide superconductor or a low-temperature metallic superconductor in terms of its behaviour in strong magnetic fields. Although the copper oxides exhibit very high transition temperatures, their in-field performance is compromized by their large anisotropy, the result of which is to restrict high bulk current densities to a region much less than the full magnetic-field-temperature (H-T) space over which superconductivity is found. Moreover, the weak coupling across grain boundaries makes transport current densities in untextured polycrystalline samples low and strongly sensitive to magnetic field. Here we report that, despite the multiphase, untextured, microscale, subdivided nature of our MgB2 samples, supercurrents flow throughout the material without exhibiting strong sensitivity to weak magnetic fields. Our combined magnetization, magneto-optical, microscopy and X-ray investigations show that the supercurrent density is mostly determined by flux pinning, rather than by the grain boundary connectivity. Our results therefore suggest that this new superconductor class is not compromized by weak-link problems, a conclusion of significance for practical applications if higher temperature analogues of this compound can be discovered. 相似文献
963.
964.
Covalent inhibition revealed by the crystal structure of the caspase-8/p35 complex 总被引:11,自引:0,他引:11
Apoptosis is a highly regulated process that is crucial for normal development and homeostasis of multicellular organisms. The p35 protein from baculoviruses effectively prevents apoptosis by its broad-spectrum caspase inhibition. Here we report the crystal structure of p35 in complex with human caspase-8 at 3.0 A resolution, and biochemical and mutagenesis studies based on the structural information. The structure reveals that the caspase is inhibited in the active site through a covalent thioester linkage to p35, which we confirmed by gel electrophoresis, hydroxylamine treatment and mass spectrometry experiments. The p35 protein undergoes dramatic conformational changes on cleavage by the caspase. The repositioning of the amino terminus of p35 into the active site of the caspase eliminates solvent accessibility of the catalytic dyad. This may be crucial for preventing hydrolysis of the thioester intermediate, which is supported by the abrogation of inhibitory activity through mutations at the N terminus of p35. The p35 protein also makes conserved contacts with the caspase outside the active-site region, providing the molecular basis for the broad-spectrum inhibitory activity of this protein. We demonstrate a new molecular mechanism of caspase inhibition, as well as protease inhibition in general. 相似文献
965.
Siddiqa A Sims-Mourtada JC Guzman-Rojas L Rangel R Guret C Madrid-Marina V Sun Y Martinez-Valdez H 《Nature》2001,410(6826):383-387
966.
967.
Integration of telomere sequences with the draft human genome sequence 总被引:15,自引:0,他引:15
Riethman HC Xiang Z Paul S Morse E Hu XL Flint J Chi HC Grady DL Moyzis RK 《Nature》2001,409(6822):948-951
Telomeres are the ends of linear eukaryotic chromosomes. To ensure that no large stretches of uncharacterized DNA remain between the ends of the human working draft sequence and the ends of each chromosome, we would need to connect the sequences of the telomeres to the working draft sequence. But telomeres have an unusual DNA sequence composition and organization that makes them particularly difficult to isolate and analyse. Here we use specialized linear yeast artificial chromosome clones, each carrying a large telomere-terminal fragment of human DNA, to integrate most human telomeres with the working draft sequence. Subtelomeric sequence structure appears to vary widely, mainly as a result of large differences in subtelomeric repeat sequence abundance and organization at individual telomeres. Many subtelomeric regions appear to be gene-rich, matching both known and unknown expressed genes. This indicates that human subtelomeric regions are not simply buffers of nonfunctional 'junk DNA' next to the molecular telomere, but are instead functional parts of the expressed genome. 相似文献
968.
969.
Most interpretations of early hominin phylogeny recognize a single early to middle Pliocene ancestral lineage, best represented by Australopithecus afarensis, which gave rise to a radiation of taxa in the late Pliocene. Here we report on new fossils discovered west of Lake Turkana, Kenya, which differ markedly from those of contemporary A. afarensis, indicating that hominin taxonomic diversity extended back, well into the middle Pliocene. A 3.5 Myr-old cranium, showing a unique combination of derived facial and primitive neurocranial features, is assigned to a new genus of hominin. These findings point to an early diet-driven adaptive radiation, provide new insight on the association of hominin craniodental features, and have implications for our understanding of Plio-Pleistocene hominin phylogeny. 相似文献
970.
Twisted gastrulation can function as a BMP antagonist 总被引:5,自引:0,他引:5
Chang C Holtzman DA Chau S Chickering T Woolf EA Holmgren LM Bodorova J Gearing DP Holmes WE Brivanlou AH 《Nature》2001,410(6827):483-487
Bone morphogenetic proteins (BMPs), including the fly homologue Decapentaplegic (DPP), are important regulators of early vertebrate and invertebrate dorsal-ventral development. An evolutionarily conserved BMP regulatory mechanism operates from fly to fish, frog and mouse to control the dorsal-ventral axis determination. Several secreted factors, including the BMP antagonist chordin/Short gastrulation (SOG), modulate the activity of BMPs. In Drosophila, Twisted gastrulation (TSG) is also involved in dorsal-ventral patterning, yet the mechanism of its function is unclear. Here we report the characterization of the vertebrate Tsg homologues. We show that Tsg can block BMP function in Xenopus embryonic explants and inhibits several ventral markers in whole-frog embryos. Tsg binds directly to BMPs and forms a ternary complex with chordin and BMPs. Coexpression of Tsg with chordin leads to a more efficient inhibition of the BMP activity in ectodermal explants. Unlike other known BMP antagonists, however, Tsg also reduces several anterior markers at late developmental stages. Our data suggest that Tsg can function as a BMP inhibitor in Xenopus; furthermore, Tsg may have additional functions during frog embryogenesis. 相似文献