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101.
Stewart CR Wilson LM Zhang Q Pham CL Waddington LJ Staples MK Stapleton D Kelly JW Howlett GJ 《Biochemistry》2007,46(18):5552-5561
Apolipoprotein amyloid deposits and lipid oxidation products are colocalized in human atherosclerotic tissue. In this study we show that the primary ozonolysis product of cholesterol, 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al (KA), rapidly promotes human apolipoprotein (apo) C-II amyloid fibril formation in vitro. Previous studies show that hydrophobic aldehydes, including KA, modify proteins by the formation of a Schiff base with the lysine epsilon-amino group or N-terminal amino group. High-performance liquid chromatography, mass spectrometry, and proteolysis of KA-modified apoC-II revealed that KA randomly modified six different lysine residues, with primarily one KA attached per apoC-II molecule. Competition experiments showed that an aldehyde scavenging compound partially inhibited the ability of KA to hasten apoC-II fibril formation. Conversely, the acid derivative of KA, lacking the ability to form a Schiff base, accelerated apoC-II fibril formation, albeit to a lesser extent, suggesting that amyloidogenesis triggered by KA involves both covalent and noncovalent mechanisms. The viability of a noncovalent mechanism mediated by KA has been observed previously with alpha-synuclein aggregation, implicated in Parkinson's disease. Electron microscopy demonstrated that fibrils formed in the presence of KA had a similar morphology to native fibrils; however, the isolated KA-apoC-II covalent adducts in the absence of unmodified apoC-II formed fibrillar structures with altered ropelike morphologies. KA-mediated fibril formation by apoC-II was inhibited by the addition of the amine-containing compound hydralazine and the lipid-binding protein apoA-I. These in vitro studies suggest that the oxidized small molecule pool could trigger or hasten the aggregation of apoC-II to form amyloid deposits. 相似文献
102.
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104.
Pham Y Li L Kim A Erdogan O Weinreb V Butterfoss GL Kuhlman B Carter CW 《Molecular cell》2007,25(6):851-862
The emergence of polypeptide catalysts for amino acid activation, the slowest step in protein synthesis, poses a significant puzzle associated with the origin of biology. This problem is compounded as the 20 contemporary aminoacyl-tRNA synthetases belong to two quite distinct families. We describe here the use of protein design to show experimentally that a minimal class I aminoacyl-tRNA synthetase active site might have functioned in the distant past. We deleted the anticodon binding domain from tryptophanyl-tRNA synthetase and fused the discontinuous segments comprising its active site. The resulting 130 residue minimal catalytic domain activates tryptophan. This residual catalytic activity constitutes the first experimental evidence that the conserved class I signature sequences, HIGH and KMSKS, might have arisen in-frame, opposite motifs 2 and 1 from class II, as complementary sense and antisense strands of the same ancestral gene. 相似文献
105.
Postsynaptic decoding of neural activity: eEF2 as a biochemical sensor coupling miniature synaptic transmission to local protein synthesis 总被引:3,自引:0,他引:3
Activity-dependent regulation of dendritic protein synthesis is critical for enduring changes in synaptic function, but how the unique features of distinct activity patterns are decoded by the dendritic translation machinery remains poorly understood. Here, we identify eukaryotic elongation factor-2 (eEF2), which catalyzes ribosomal translocation during protein synthesis, as a biochemical sensor in dendrites that is specifically and locally tuned to the quality of neurotransmission. We show that intrinsic action potential (AP)-mediated network activity in cultured hippocampal neurons maintains eEF2 in a relatively dephosphorylated (active) state, whereas spontaneous neurotransmitter release (i.e., miniature neurotransmission) strongly promotes the phosphorylation (and inactivation) of eEF2. The regulation of eEF2 phosphorylation is responsive to bidirectional changes in miniature neurotransmission and is controlled locally in dendrites. Finally, direct spatially controlled inhibition of eEF2 phosphorylation induces local translational activation, suggesting that eEF2 is a biochemical sensor that couples miniature synaptic events to local translational suppression in neuronal dendrites. 相似文献
106.
Binh Tran Quang Linh Duong Tuan Chung Le Thi Kim Phuong Pham Tran Nga Bui Thi Thuy Ngoc Nguyen Anh Thuyen Tran Quang Tung Do Dinh Nhung Bui Thi 《Biochemical genetics》2022,60(2):707-719
Biochemical Genetics - The study aimed to evaluate the contribution of the FTO A/T polymorphism (rs9939609) to the prediction of the future type 2 diabetes (T2D). A population-based prospective... 相似文献
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108.
Jean-Pierre Dujardin Truong Xuan Lam Pham Thi Khoa Christopher John Schofield 《Memórias do Instituto Oswaldo Cruz》2015,110(3):319-323
The migration of invasive vector species has contributed to the worldwide extension
of infectious diseases such as dengue (Aedes aegypti) and chikungunya (Aedes
albopictus). It is probably a similar behaviour for certain vectors of Chagas disease
which allowed it to become a continental burden in Latin America. One of them,
Triatoma rubrofasciata has also been spreading throughout the tropical and
subtropical world. Here, the recent and massive peridomestic presence of T.
rubrofasciata in Vietnam cities is reported, and tentatively explained, highlighting
the need for improved entomological surveillance. 相似文献
109.
A new species, Hoya hanhiae V. T. Pham et Aver. discovered in central Vietnam is described, illustrated and compared with the related species H. macrophylla Bl. and H. verticillata (Vahl) G. Don. 相似文献