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排序方式: 共有266条查询结果,搜索用时 31 毫秒
21.
Tumour necrosis factor (TNF)-receptor-associated factors (TRAFs) form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily and the interleukin-1 receptor. They are important in the regulation of cell survival and cell death. The carboxy-terminal region of TRAFs (the TRAF domain) is required for self-association and interaction with receptors. The domain contains a predicted coiled-coil region that is followed by a highly conserved TRAF-C domain. Here we report the crystal structure of the TRAF domain of human TRAF2, both alone and in complex with a peptide from TNF receptor-2 (TNF-R2). The structures reveal a trimeric self-association of the TRAF domain, which we confirm by studies in solution. The TRAF-C domain forms a new, eight-stranded antiparallel beta-sandwich structure. The TNF-R2 peptide binds to a conserved shallow surface depression on one TRAF-C domain and does not contact the other protomers of the trimer. The nature of the interaction indicates that an SXXE motif may be a TRAF2-binding consensus sequence. The trimeric structure of the TRAF domain provides an avidity-based explanation for the dependence of TRAF recruitment on the oligomerization of the receptors by their trimeric extracellular ligands. 相似文献
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Birth of parthenogenetic mice that can develop to adulthood 总被引:1,自引:0,他引:1
Only mammals have relinquished parthenogenesis, a means of producing descendants solely from maternal germ cells. Mouse parthenogenetic embryos die by day 10 of gestation. Bi-parental reproduction is necessary because of parent-specific epigenetic modification of the genome during gametogenesis. This leads to unequal expression of imprinted genes from the maternal and paternal alleles. However, there is no direct evidence that genomic imprinting is the only barrier to parthenogenetic development. Here we show the development of a viable parthenogenetic mouse individual from a reconstructed oocyte containing two haploid sets of maternal genome, derived from non-growing and fully grown oocytes. This development was made possible by the appropriate expression of the Igf2 and H19 genes with other imprinted genes, using mutant mice with a 13-kilobase deletion in the H19 gene as non-growing oocytes donors. This full-term development is associated with a marked reduction in aberrantly expressed genes. The parthenote developed to adulthood with the ability to reproduce offspring. These results suggest that paternal imprinting prevents parthenogenesis, ensuring that the paternal contribution is obligatory for the descendant. 相似文献
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Coulomb blockade and the Kondo effect in single-atom transistors 总被引:7,自引:0,他引:7
Park J Pasupathy AN Goldsmith JI Chang C Yaish Y Petta JR Rinkoski M Sethna JP Abruña HD McEuen PL Ralph DC 《Nature》2002,417(6890):722-725
Using molecules as electronic components is a powerful new direction in the science and technology of nanometre-scale systems. Experiments to date have examined a multitude of molecules conducting in parallel, or, in some cases, transport through single molecules. The latter includes molecules probed in a two-terminal geometry using mechanically controlled break junctions or scanning probes as well as three-terminal single-molecule transistors made from carbon nanotubes, C(60) molecules, and conjugated molecules diluted in a less-conducting molecular layer. The ultimate limit would be a device where electrons hop on to, and off from, a single atom between two contacts. Here we describe transistors incorporating a transition-metal complex designed so that electron transport occurs through well-defined charge states of a single atom. We examine two related molecules containing a Co ion bonded to polypyridyl ligands, attached to insulating tethers of different lengths. Changing the length of the insulating tether alters the coupling of the ion to the electrodes, enabling the fabrication of devices that exhibit either single-electron phenomena, such as Coulomb blockade, or the Kondo effect. 相似文献
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Fabry - Perot interference in a nanotube electron waveguide 总被引:9,自引:0,他引:9
The behaviour of traditional electronic devices can be understood in terms of the classical diffusive motion of electrons. As the size of a device becomes comparable to the electron coherence length, however, quantum interference between electron waves becomes increasingly important, leading to dramatic changes in device properties. This classical-to-quantum transition in device behaviour suggests the possibility for nanometer-sized electronic elements that make use of quantum coherence. Molecular electronic devices are promising candidates for realizing such device elements because the electronic motion in molecules is inherently quantum mechanical and it can be modified by well defined chemistry. Here we describe an example of a coherent molecular electronic device whose behaviour is explicitly dependent on quantum interference between propagating electron waves-a Fabry-Perot electron resonator based on individual single-walled carbon nanotubes with near-perfect ohmic contacts to electrodes. In these devices, the nanotubes act as coherent electron waveguides, with the resonant cavity formed between the two nanotube-electrode interfaces. We use a theoretical model based on the multichannel Landauer-Büttiker formalism to analyse the device characteristics and find that coupling between the two propagating modes of the nanotubes caused by electron scattering at the nanotube-electrode interfaces is important. 相似文献
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Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion 总被引:17,自引:0,他引:17
Potocki L Chen KS Park SS Osterholm DE Withers MA Kimonis V Summers AM Meschino WS Anyane-Yeboa K Kashork CD Shaffer LG Lupski JR 《Nature genetics》2000,24(1):84-87
Recombination between repeated sequences at various loci of the human genome are known to give rise to DNA rearrangements associated with many genetic disorders. Perhaps the most extensively characterized genomic region prone to rearrangement is 17p12, which is associated with the peripheral neuropathies, hereditary neuropathy with liability to pressure palsies (HNPP) and Charcot-Marie-Tooth disease type 1A (CMT1A;ref. 2). Homologous recombination between 24-kb flanking repeats, termed CMT1A-REPs, results in a 1.5-Mb deletion that is associated with HNPP, and the reciprocal duplication product is associated with CMT1A (ref. 2). Smith-Magenis syndrome (SMS) is a multiple congenital anomalies, mental retardation syndrome associated with a chromosome 17 microdeletion, del(17)(p11.2p11.2) (ref. 3,4). Most patients (>90%) carry deletions of the same genetic markers and define a common deletion. We report seven unrelated patients with de novo duplications of the same region deleted in SMS. A unique junction fragment, of the same apparent size, was identified in each patient by pulsed field gel electrophoresis (PFGE). Further molecular analyses suggest that the de novo17p11.2 duplication is preferentially paternal in origin, arises from unequal crossing over due to homologous recombination between flanking repeat gene clusters and probably represents the reciprocal recombination product of the SMS deletion. The clinical phenotype resulting from duplication [dup(17)(p11.2p11.2)] is milder than that associated with deficiency of this genomic region. This mechanism of reciprocal deletion and duplication via homologous recombination may not only pertain to the 17p11.2 region, but may also be common to other regions of the genome where interstitial microdeletion syndromes have been defined. 相似文献
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CD1-restricted T-cell responses and microbial infection 总被引:11,自引:0,他引:11
CD1, a conserved family of major histocompatibility (MHC)-like glycoproteins in mammals, specializes in capturing lipid rather than peptide antigen for presentation to T lymphocytes. The principles and mechanisms of this newly discovered immune strategy differ markedly from those governing classical MHC-peptide presentation. They might be exploited for the design of new lipid-based microbial vaccines and adjuvants. 相似文献
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