全文获取类型
收费全文 | 719篇 |
免费 | 147篇 |
国内免费 | 1篇 |
专业分类
867篇 |
出版年
2021年 | 9篇 |
2018年 | 9篇 |
2016年 | 14篇 |
2015年 | 18篇 |
2014年 | 22篇 |
2013年 | 25篇 |
2012年 | 34篇 |
2011年 | 22篇 |
2010年 | 24篇 |
2009年 | 18篇 |
2008年 | 15篇 |
2007年 | 19篇 |
2006年 | 16篇 |
2005年 | 13篇 |
2004年 | 15篇 |
2003年 | 14篇 |
2002年 | 15篇 |
2001年 | 24篇 |
2000年 | 18篇 |
1999年 | 24篇 |
1998年 | 25篇 |
1997年 | 21篇 |
1996年 | 13篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 12篇 |
1992年 | 17篇 |
1991年 | 21篇 |
1990年 | 21篇 |
1989年 | 17篇 |
1988年 | 18篇 |
1987年 | 10篇 |
1986年 | 16篇 |
1985年 | 16篇 |
1984年 | 11篇 |
1983年 | 15篇 |
1982年 | 13篇 |
1981年 | 13篇 |
1980年 | 10篇 |
1979年 | 13篇 |
1978年 | 14篇 |
1977年 | 24篇 |
1976年 | 20篇 |
1975年 | 14篇 |
1974年 | 9篇 |
1973年 | 15篇 |
1972年 | 13篇 |
1971年 | 9篇 |
1968年 | 13篇 |
1966年 | 11篇 |
排序方式: 共有867条查询结果,搜索用时 15 毫秒
11.
95-kilodalton B-Raf serine/threonine kinase: identification of the protein and its major autophosphorylation site. 总被引:4,自引:0,他引:4 下载免费PDF全文
R M Stephens G Sithanandam T D Copeland D R Kaplan U R Rapp D K Morrison 《Molecular and cellular biology》1992,12(9):3733-3742
B-Raf, a member of the Raf family of serine/threonine kinases, is expressed primarily in the brain and in the nervous system. In this study, the biochemical properties of the B-Raf protein were investigated in nerve growth factor (NGF)-responsive cell lines and in brain tissues. B-Raf was identified by using phosphopeptide mapping analysis and cDNA analysis as a 95-kDa protein which is primarily localized in the cytosol. NGF rapidly stimulated both serine and threonine phosphorylation in vivo and autophosphorylation activity in vitro of the B-Raf protein. In PC12 cells, B-Raf autokinase activity was induced by both differentiation factors and mitogens, with maximal activity observed after 5 min of factor addition. B-Raf kinase activity was also observed following NGF treatment of SH-SY5Y neuroblastoma cells and in adult mouse brain and hippocampus. Induction of B-Raf kinase activity in NGF-treated PC12 cells required expression of kinase-active trk receptors. Exogenous substrates or a peptide containing the autophosphorylation site became phosphorylated when added to immune complex kinase assays and reduced the in vitro autophosphorylation activity of B-Raf, suggesting that in vitro autophosphorylation sites and exogenous substrates compete for active sites of the B-Raf kinase. Finally, the major in vitro autophosphorylation site of B-Raf was identified as threonine 372 in the conserved region 2 domain. A threonine residue is present at similar positions in all three mammalian Raf family members and may represent a regulatory site for these proteins. 相似文献
12.
Epidermal growth factor (EGF) stimulates association and kinase activity of Raf-1 with the EGF receptor. 总被引:16,自引:8,他引:8 下载免费PDF全文
H App R Hazan A Zilberstein A Ullrich J Schlessinger U Rapp 《Molecular and cellular biology》1991,11(2):913-919
Raf-1 serine- and threonine-specific protein kinase is transiently activated in cells expressing the epidermal growth factor (EGF) receptor upon treatment with EGF. The stimulated EGF receptor coimmunoprecipitates with Raf-1 kinase and mediates protein kinase C-independent phosphorylation of Raf-1 on serine residues. Hyperphosphorylated Raf-1 has lower mobility on sodium dodecyl sulfate gels and has sixfold-increased activity in immunocomplex kinase assay with histone H1 or Raf-1 sequence-derived peptide as a substrate. Raf-1 activation requires kinase-active EGF receptor; a point mutant lacking tyrosine kinase activity in inactive in Raf-1 coupling and association. It is noteworthy that tyrosine phosphorylation of c-Raf-1 induced by EGF was not detected in these cells. These observations suggest that Raf-1 kinase may act as an important downstream effector of EGF signal transduction. 相似文献
13.
In this report we describe the expression of v-raf protein in E. coli using a tryptophan-promoter-driven expression vector and its immunological characterization by anti-peptide sera. The purified recombinant protein was used to produce raf-specific antibodies which are suitable for studying v-raf and c-raf proteins in vitro and in vivo in a variety of species ranging from mouse to man. 相似文献
14.
Wolfgang Hagmann Claudio Denzlinger Stephan Rapp Gisbert Weckbecker Dietrich Keppler 《Prostaglandins & other lipid mediators》1986,31(2)
Mercapturic acid formation, an established pathway in the detoxication of xenobiotics, is demonstrated for cysteinyl leukotrienes generated in rats
after endotoxin treatment. The mercapturate N-acetyl-leukotriene E4 (N-acetyl-LTE4) represented a major metabolite eliminated into bile after injection of [3H]LTC4 as shown by cochromatography with synthetic N-acetyl-LTE4 in four different HPLC solvent systems. The identity of endogenoud N-acetyl-LTE4 elicited by endotoxin
was additionally verified by enzymatic deacetylation followed by chemical N-acetylation. The deacetylation was catalyzed by penicillin amidase. Endogenous cysteinyl leukotrienes were quantified by radioimmunoassay after HPLC separation. A N-acetyl-LTE4 concentration of 80 nmol/l was determined in bile collected between 30 and 60 min after endotoxin injection. Under this condition, other cysteinyl leukotrienes detected in bile by radioimmunoassay amounted to less than 5% of N-acetyl-LTE4. The mercapturic acid pathway, leading from the glutathione conjugate LTC4 to N-acetyl-LTE4, thus plays an important role in the deactivation and elimination of these potent endogenous mediators. 相似文献
15.
P E Rapp 《Biology of reproduction》1985,32(1):70-72
Two statements will be presented and defended in this paper. First, it is claimed that oscillations are common in all biological systems. From the subcellular to the organismic levels of organization, oscillations are the normal operational mode for many biochemical and physiological control networks. Second, it will be demonstrated that periodic control offers several functional advantages over steady-state control. 相似文献
16.
17.
Methods for computing the standard errors of branching points in an evolutionary tree and their application to molecular data from humans and apes 总被引:23,自引:2,他引:21
Statistical methods for computing the standard errors of the branching
points of an evolutionary tree are developed. These methods are for the
unweighted pair-group method-determined (UPGMA) trees reconstructed from
molecular data such as amino acid sequences, nucleotide sequences,
restriction-sites data, and electrophoretic distances. They were applied to
data for the human, chimpanzee, gorilla, orangutan, and gibbon species.
Among the four different sets of data used, DNA sequences for an
895-nucleotide segment of mitochondrial DNA (Brown et al. 1982) gave the
most reliable tree, whereas electrophoretic data (Bruce and Ayala 1979)
gave the least reliable one. The DNA sequence data suggested that the
chimpanzee is the closest and that the gorilla is the next closest to the
human species. The orangutan and gibbon are more distantly related to man
than is the gorilla. This topology of the tree is in agreement with that
for the tree obtained from chromosomal studies and DNA-hybridization
experiments. However, the difference between the branching point for the
human and the chimpanzee species and that for the gorilla species and the
human-chimpanzee group is not statistically significant. In addition to
this analysis, various factors that affect the accuracy of an estimated
tree are discussed.
相似文献
18.
The rheological behavior of cultures of Cellulomonas uda with shredded printed newspaper as the carbon source was studied. The initial substrate concentrations ranged from 23 to 60 g/L. The changes in apparent viscosity were followed on-line by applying a commercially available process viscometer and discretely using a rotational viscometer with an anchor impeller. During the time of highest cellulose degradation, the broths exhibited a pseudoplastic behavior which could be explained satisfactorily by the power-law model. At the end of cultivation when cellulose degradation slowed down, the broths became Newtonian in behavior. Endo-1,4-beta-glucanase, 1,4-beta-xylanase, beta-glucosidase, and beta-xylosidase activities were also determined during cultivation as well as cellulose degradation and cell mass production. The beginning of endoglucanase formation and the start of the final viscosity decrease of the bacterial paper pulp suspensions could be correlated. 相似文献
19.
The ammonium uptake system of Rhodobacter capsulatus B100 was examined using the ammonium analog methylammonium. This analog was not transported when cells were grown aerobically on ammonium. When cultured on glutamate as a nitrogen source, or when nitrogen-starved, cells would take up methylammonium. Therefore, in cells grown under nitrogen-limiting conditions, a second system of ammonium uptake (or a modified form of the first) is present which is distinguished by its capacity for transporting the analog in addition to ammonium. The methylammonium uptake system exhibited saturation kinetics with a K
m of 22 M and a V
max of about 3 nmol per min · mg protein. Ammonium completely inhibited analog transport with a K
i in the range of 1 M. Once inside the cell methylammonium was rapidly converted to -N-methylglutamine; however, a small concentration gradient of methylammonium could still be observed. Kinetic parameters reflect the effects of assimilation.The methylammonium uptake system was temperature and pH dependent, and inhibition studies indicated that energy was required for the system to be operative. A glutamine auxotroph (G29) lacking the structural gene for glutanime synthetase did not accumulate the analog, even when nitrogen starved. The Nif- mutant J61, which is unable to express nitrogenase structural genes, also did not transport methylammonium, regardless of the nitrogen source for growth. However, the mutant exhibited wild-type ammonium uptake and glutamine synthetase activity. These data suggest that transport of ammonium is required for growth on limited nitrogen and is under the control of the Ntr system in R. capsulatus.Abbreviations CCCP
carbonyl cyanide-m-chlorophenyl hydrazone
- CHES
cyclohexylaminoethanesulfonic acid
- DMSO
dimethyl sulfoxide
- GMAD
-N-methylglutamine
- GS
glutamine synthetase
- MES
2-(N-morpholino) ethanesulfonic acid
- MSX
methionine-Dl-sulfoximine
- pCMB
p-chloromercuribenzoate
- Tricine
N-tris(hydroxymethyl)methylglycine 相似文献
20.
The complete coding sequence of the human raf oncogene and the corresponding structure of the c-raf-1 gene. 总被引:36,自引:4,他引:32 下载免费PDF全文
T I Bonner H Oppermann P Seeburg S B Kerby M A Gunnell A C Young U R Rapp 《Nucleic acids research》1986,14(2):1009-1015
The complete 648 amino acid sequence of the human raf oncogene was deduced from the 2977 nucleotide sequence of a fetal liver cDNA. The cDNA has been used to obtain clones which extend the human c-raf-1 locus by an additional 18.9 kb at the 5' end and contain all the remaining coding exons. 相似文献