全文获取类型
收费全文 | 1250篇 |
免费 | 88篇 |
出版年
2022年 | 15篇 |
2021年 | 22篇 |
2020年 | 8篇 |
2019年 | 11篇 |
2018年 | 31篇 |
2017年 | 12篇 |
2016年 | 20篇 |
2015年 | 44篇 |
2014年 | 62篇 |
2013年 | 57篇 |
2012年 | 92篇 |
2011年 | 93篇 |
2010年 | 56篇 |
2009年 | 54篇 |
2008年 | 66篇 |
2007年 | 87篇 |
2006年 | 72篇 |
2005年 | 68篇 |
2004年 | 49篇 |
2003年 | 49篇 |
2002年 | 81篇 |
2001年 | 10篇 |
2000年 | 11篇 |
1999年 | 6篇 |
1998年 | 24篇 |
1997年 | 17篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1994年 | 7篇 |
1993年 | 11篇 |
1992年 | 14篇 |
1991年 | 13篇 |
1990年 | 6篇 |
1989年 | 11篇 |
1988年 | 7篇 |
1987年 | 9篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 11篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1977年 | 5篇 |
1976年 | 11篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 5篇 |
1971年 | 8篇 |
1969年 | 5篇 |
排序方式: 共有1338条查询结果,搜索用时 31 毫秒
61.
Klumpp S Bechmann G Mäurer A Selke D Krieglstein J 《Biochemical and biophysical research communications》2003,306(1):110-115
The first protein histidine phosphatase from vertebrates discovered recently was found in a variety of tissues, however, a physiological substrate protein was missing. Phosphorylation of liver extracts in the presence of EDTA, followed by SDS-PAGE and autoradiography showed labeling of three proteins. Acid- and alkaline-treatment revealed the existence of N-phosphates. Addition of histidine phosphatase exclusively resulted in dephosphorylation of a 110kDa protein (denaturing conditions). Gelfiltration revealed its native molecular mass of approximately 450kDa. That protein was purified and identified as ATP-citrate lyase. The results are in favor of histidine phosphatase playing an important yet unidentified role in metabolic processes. 相似文献
62.
63.
Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2) 总被引:3,自引:0,他引:3
Werz O Szellas D Steinhilber D Rådmark O 《The Journal of biological chemistry》2002,277(17):14793-14800
We demonstrated previously that 5-lipoxygenase (5-LO), a key enzyme in leukotriene biosynthesis, can be phosphorylated by p38 MAPK-regulated MAPKAP kinases (MKs). Here we show that mutation of Ser-271 to Ala in 5-LO abolished MK2 catalyzed phosphorylation and clearly reduced phosphorylation by kinases prepared from stimulated polymorphonuclear leukocytes and Mono Mac 6 cells. Compared with heat shock protein 27 (Hsp-27), 5-LO was a weak substrate for MK2. However, the addition of unsaturated fatty acids (i.e. arachidonate 1-50 microm) up-regulated phosphorylation of 5-LO, but not of Hsp-27, by active MK2 in vitro, resulting in a similar phosphorylation as for Hsp-27. 5-LO was phosphorylated also by other serine/threonine kinases recognizing the motif Arg-Xaa-Xaa-Ser (protein kinase A, Ca(2+)/calmodulin-dependent kinase II), but these activities were not increased by fatty acids. HeLa cells expressing wild type 5-LO or S271A-5-LO, showed prominent 5-LO activity when incubated with Ca(2+)-ionophore plus arachidonate. However, when stimulated with only exogenous arachidonic acid, activity for the S271A mutant was significantly lower as compared with wild type 5-LO. It appears that phosphorylation at Ser-271 is more important for 5-LO activity induced by a stimulus that does not prominently increase intracellular Ca(2+) and that arachidonic acid stimulates leukotriene biosynthesis also by promoting this MK2-catalyzed phosphorylation. 相似文献
64.
65.
Vibrio cholerae phage K139: complete genome sequence and comparative genomics of related phages 下载免费PDF全文
In this report, we characterize the complete genome sequence of the temperate phage K139, which morphologically belongs to the Myoviridae phage family (P2 and 186). The prophage genome consists of 33,106 bp, and the overall GC content is 48.9%. Forty-four open reading frames were identified. Homology analysis and motif search were used to assign possible functions for the genes, revealing a close relationship to P2-like phages. By Southern blot screening of a Vibrio cholerae strain collection, two highly K139-related phage sequences were detected in non-O1, non-O139 strains. Combinatorial PCR analysis revealed almost identical genome organizations. One region of variable gene content was identified and sequenced. Additionally, the tail fiber genes were analyzed, leading to the identification of putative host-specific sequence variations. Furthermore, a K139-encoded Dam methyltransferase was characterized. 相似文献
66.
67.
The slow-evolving mitochondrial DNAs of plants have potentially conserved information on the phylogenetic branching of the
earliest land plants. We present the nad2 gene structures in hornworts and liverworts and in the presumptive earliest-branching
vascular land plant clade, the Lycopodiopsida. Taken together with the recently obtained nad2 data for mosses, each class
of bryophytes presents another pattern of angiosperm-type introns conserved in nad2: intron nad2i1 in mosses; intron nad2i3
in liverworts; and both introns, nad2i3 and nad2i4, in hornworts. The lycopods Isoetes and Lycopodium show diverging intron
conservation and feature a unique novel intron, termed nad2i3b. Hence, mitochondrial introns in general are positionally stable
in the bryophytes and provide significant intraclade phylogenetic information, but the nad2 introns, in particular, cannot
resolve the interclade relationships of the bryophyte classes and to the tracheophytes. The necessity for RNA editing to reconstitute
conserved codon entities in nad2 is obvious for all clades except the marchantiid liverworts. Finally, we find that particularly
small group II introns appear as a general feature of the Isoetes chondriome. Plant mitochondrial peculiarities such as RNA
editing frequency, U-to-C type of RNA editing, and small group II introns appear to be genus-specific rather than gene-specific
features. 相似文献
68.
We present a mathematical model which reproduces experimental data on the germinal centre (GC) kinetics of the primed primary immune response and on affinity maturation observed during the reaction. We show that antigen masking by antibodies which are produced by emerging plasma cells can drive affinity maturation and provide a feedback mechanism by which the reaction is stable against variations in the initial antigen amount over several orders of magnitude. This provides a possible answer to the long-standing question of the role of antigen reduction in driving affinity maturation. By comparing model predictions with experimental results, we propose that the selection probability of centrocytes and the recycling probability of selected centrocytes are not constant but vary during the GC reaction with respect to time. It is shown that the efficiency of affinity maturation is highest if clones with an affinity for the antigen well above the average affinity in the GC leave the GC for either the memory or plasma cell pool. It is further shown that termination of somatic hypermutation several days before the end of the germinal centre reaction is beneficial for affinity maturation. The impact on affinity maturation of simultaneous initiation of memory cell formation and somatic hypermutation vs. delayed initiation of memory cell formation is discussed. 相似文献
69.
Gruffat H Batisse J Pich D Neuhierl B Manet E Hammerschmidt W Sergeant A 《Journal of virology》2002,76(19):9635-9644
The splicing machinery which positions a protein export complex near the exon-exon junction mediates nuclear export of mRNAs generated from intron-containing genes. Many Epstein-Barr virus (EBV) early and late genes are intronless, and an alternative pathway, independent of splicing, must export the corresponding mRNAs. Since the EBV EB2 protein induces the cytoplasmic accumulation of intronless mRNA, it is tempting to speculate that EB2 is a viral adapter involved in the export of intronless viral mRNA. If this is true, then the EB2 protein is essential for the production of EBV infectious virions. To test this hypothesis, we generated an EBV mutant in which the BMLF1 gene, encoding the EB2 protein, has been deleted (EBV(BMLF1-KO)). Our studies show that EB2 is necessary for the production of infectious EBV and that its function cannot be transcomplemented by a cellular factor. In the EBV(BMLF1-KO) 293 cells, oriLyt-dependent DNA replication was greatly enhanced by EB2. Accordingly, EB2 induced the cytoplasmic accumulation of a subset of EBV early mRNAs coding for essential proteins implicated in EBV DNA replication during the productive cycle. Two herpesvirus homologs of the EB2 protein, the herpes simplex virus type 1 protein ICP27 and, the human cytomegalovirus protein UL69, only partly rescued the phenotype of the EBV(BMLF1-KO) mutant, indicating that some EB2 functions in virus production cannot be transcomplemented by ICP27 and UL69. 相似文献
70.