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91.
Regulation of p53 activity through lysine methylation 总被引:1,自引:0,他引:1
Chuikov S Kurash JK Wilson JR Xiao B Justin N Ivanov GS McKinney K Tempst P Prives C Gamblin SJ Barlev NA Reinberg D 《Nature》2004,432(7015):353-360
p53 is a tumour suppressor that regulates the cellular response to genotoxic stresses. p53 is a short-lived protein and its activity is regulated mostly by stabilization via different post-translational modifications. Here we report a novel mechanism of p53 regulation through lysine methylation by Set9 methyltransferase. Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region. Methylated p53 is restricted to the nucleus and the modification positively affects its stability. Set9 regulates the expression of p53 target genes in a manner dependent on the p53-methylation site. The crystal structure of a ternary complex of Set9 with a p53 peptide and the cofactor product S-adenosyl-l-homocysteine (AdoHcy) provides the molecular basis for recognition of p53 by this lysine methyltransferase. 相似文献
92.
Biologically active natural products often contain particularly challenging structural features and functionalities in terms of synthesis. Perhaps the greatest difficulties are those caused by issues of stereochemistry. A useful strategy for synthesizing such molecules is to devise methods of bond formation that provide opportunities for using enantioselective catalysis. In using this tactic, the desire for a particular target structure ultimately drives the development of catalytic methods. New enantioselective catalytic methods contribute to a greater fundamental understanding of how bonds can be constructed and lead to valuable synthetic technologies that are useful for a variety of applications. 相似文献
93.
Abreu-Blanco MT Watts JJ Verboon JM Parkhurst SM 《Cellular and molecular life sciences : CMLS》2012,69(15):2469-2483
Wound repair on the cellular and multicellular levels is essential to the survival of complex organisms. In order to avoid further damage, prevent infection, and restore normal function, cells and tissues must rapidly seal and remodel the wounded area. The cytoskeleton is an important component of wound repair in that it is needed for actomyosin contraction, recruitment of repair machineries, and cell migration. Recent use of model systems and high-resolution microscopy has provided new insight into molecular aspects of the cytoskeletal response during wound repair. Here we discuss the role of the cytoskeleton in single-cell, embryonic, and adult repair, as well as the striking resemblance of these processes to normal developmental events and many diseases. 相似文献
94.
95.
Sloan JL Johnston JJ Manoli I Chandler RJ Krause C Carrillo-Carrasco N Chandrasekaran SD Sysol JR O'Brien K Hauser NS Sapp JC Dorward HM Huizing M;NIH Intramural Sequencing Center Group Barshop BA Berry SA James PM Champaigne NL de Lonlay P Valayannopoulos V Geschwind MD Gavrilov DK Nyhan WL Biesecker LG Venditti CP 《Nature genetics》2011,43(9):883-886
We used exome sequencing to identify the genetic basis of combined malonic and methylmalonic aciduria (CMAMMA). We sequenced the exome of an individual with CMAMMA and followed up with sequencing of eight additional affected individuals (cases). This included one individual who was identified and diagnosed by searching an exome database. We identify mutations in ACSF3, encoding a putative methylmalonyl-CoA and malonyl-CoA synthetase as a cause of CMAMMA. We also examined a canine model of CMAMMA, which showed pathogenic mutations in a predicted ACSF3 ortholog. ACSF3 mutant alleles occur with a minor allele frequency of 0.0058 in ~1,000 control individuals, predicting a CMAMMA population incidence of ~1:30,000. ACSF3 deficiency is the first human disorder identified as caused by mutations in a gene encoding a member of the acyl-CoA synthetase family, a diverse group of evolutionarily conserved proteins, and may emerge as one of the more common human metabolic disorders. 相似文献
96.
Lennart Zabeau Cathy J. Jensen Sylvie Seeuws Koen Venken Annick Verhee Dominiek Catteeuw Geert van Loo Hui Chen Ken Walder Jacob Hollis Simon Foote Margaret J. Morris José Van der Heyden Frank Peelman Brian J. Oldfield Justin P. Rubio Dirk Elewaut Jan Tavernier 《Cellular and molecular life sciences : CMLS》2015,72(3):629-644
97.
Occurrences of mountain lions ( Puma concolor ) in Nebraska have been steadily increasing; however, reproductive activity in mountain lions has not been documented in the state. We present the first evidence of mountain lion reproduction in Nebraska since mountain lions recolonized the state in the early 1990s. On 28 February 2007, a spotted kitten was hit by a vehicle in northwestern Nebraska; and based on body length and weight, we estimate its age at 3.9 months. On 20 December 2008, a female mountain lion and spotted kitten were photographed in the northwestern part of the state. On 9 May 2009, a female mountain lion with a juvenile was also photographed. All records were from the Pine Ridge region of Dawes County, Nebraska. Our records suggest that mountain lions are establishing a permanent population in at least one region of Nebraska. 相似文献
98.
The traditional view of cortical visual processing is that primary visual cortex (V1) analyzes simple visual attributes, and that object recognition involves a progressive “complexification” of receptive field (RF) properties along the visual pathway extending into the temporal lobe. Based on our studies with a combination of electrophysiological, imaging, psychophysical and computational approaches, we find to the contrary that V1 is capable of encoding much more complex stimulus features than originally believed, and that it can integrate information over large parts of the visual field. Moreover, V1 is continually involved in encoding information about learned stimulus configurations under top-down influences specific to the trained perceptual task. 相似文献
99.
Barouch DH Liu J Li H Maxfield LF Abbink P Lynch DM Iampietro MJ SanMiguel A Seaman MS Ferrari G Forthal DN Ourmanov I Hirsch VM Carville A Mansfield KG Stablein D Pau MG Schuitemaker H Sadoff JC Billings EA Rao M Robb ML Kim JH Marovich MA Goudsmit J Michael NL 《Nature》2012,482(7383):89-93
Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIV(SME543) Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection against repetitive, intrarectal SIV(MAC251) challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys. 相似文献
100.