全文获取类型
收费全文 | 1906篇 |
免费 | 47篇 |
国内免费 | 37篇 |
出版年
2023年 | 14篇 |
2022年 | 18篇 |
2021年 | 21篇 |
2020年 | 23篇 |
2019年 | 37篇 |
2018年 | 54篇 |
2017年 | 17篇 |
2016年 | 19篇 |
2015年 | 54篇 |
2014年 | 93篇 |
2013年 | 112篇 |
2012年 | 91篇 |
2011年 | 124篇 |
2010年 | 78篇 |
2009年 | 65篇 |
2008年 | 76篇 |
2007年 | 76篇 |
2006年 | 84篇 |
2005年 | 75篇 |
2004年 | 64篇 |
2003年 | 61篇 |
2002年 | 68篇 |
2001年 | 51篇 |
2000年 | 18篇 |
1999年 | 28篇 |
1998年 | 35篇 |
1997年 | 29篇 |
1996年 | 33篇 |
1995年 | 26篇 |
1994年 | 29篇 |
1993年 | 13篇 |
1992年 | 27篇 |
1991年 | 16篇 |
1990年 | 25篇 |
1989年 | 16篇 |
1988年 | 18篇 |
1987年 | 15篇 |
1986年 | 9篇 |
1985年 | 34篇 |
1984年 | 39篇 |
1983年 | 27篇 |
1982年 | 34篇 |
1981年 | 26篇 |
1980年 | 18篇 |
1979年 | 20篇 |
1978年 | 23篇 |
1977年 | 11篇 |
1976年 | 16篇 |
1975年 | 12篇 |
1974年 | 8篇 |
排序方式: 共有1990条查询结果,搜索用时 687 毫秒
1.
D. S. Coffman Ben H. Leichtling H. V. Rickenberg 《Journal of cellular biochemistry》1981,15(4):369-385
The phosphoproteins of Dictyostelium discoideum were compared at different stages of development by polyacrylamide gel electrophoresis. Certain phosphoproteins of vegetative amoebae were conserved while others appeared and disappeared during development. Four major phosphoproteins with apparent subunit molecular weights of 50,000, 47,000, 38,000, and 34,000 disappeared precociously in response to exogenous cAMP. Two membranal phosphoproteins, with apparent subunit molecular weights of 80,000 and 81,000, appeared precociously in response to added cAMP. One of these phosphoproteins, molecular weight of 80,000, has been identified tentatively as the “contact site A” glycoprotein. Another membranal protein, with apparent subunit molecular weight of 42,000, unaffected in its appearance by cAMP, has been identified tentatively as phosphoactin. 相似文献
2.
A method is described for the subcellular fractionation of goldfish xanthophores. The procedure produces relatively pure fractions of caroteniod droplets, pterinosomes, cytosol and what appears to be plasma membrane. The presence of a distinct pattern of proteins is shown to be associated with the carotenoid droplets. Treatment of the xanthophores with ACTH affects the buoyant density of some carotenoid droplets and stimulates the phosphorylation of a polypeptide associated with the carotenoid droplets. 相似文献
3.
4.
Teresa K. Aman Bruce A. Maki Thomas J. Ruffino Eileen M. Kasperek Gabriela K. Popescu 《The Journal of biological chemistry》2014,289(27):18805-18817
Protein kinase A (PKA) enhances synaptic plasticity in the central nervous system by increasing NMDA receptor current amplitude and Ca2+ flux in an isoform-dependent yet poorly understood manner. PKA phosphorylates multiple residues on GluN1, GluN2A, and GluN2B subunits in vivo, but the functional significance of this multiplicity is unknown. We examined gating and permeation properties of recombinant NMDA receptor isoforms and of receptors with altered C-terminal domain (CTDs) prior to and after pharmacological inhibition of PKA. We found that PKA inhibition decreased GluN1/GluN2B but not GluN1/GluN2A gating; this effect was due to slower rates for receptor activation and resensitization and was mediated exclusively by the GluN2B CTD. In contrast, PKA inhibition reduced NMDA receptor-relative Ca2+ permeability (PCa/PNa) regardless of the GluN2 isoform and required the GluN1 CTD; this effect was due primarily to decreased unitary Ca2+ conductance, because neither Na+ conductance nor Ca2+-dependent block was altered substantially. Finally, we show that both the gating and permeation effects can be reproduced by changing the phosphorylation state of a single residue: GluN2B Ser-1166 and GluN1 Ser-897, respectively. We conclude that PKA effects on NMDA receptor gating and Ca2+ permeability rely on distinct phosphorylation sites located on the CTD of GluN2B and GluN1 subunits. This separate control of NMDA receptor properties by PKA may account for the specific effects of PKA on plasticity during synaptic development and may lead to drugs targeted to alter NMDA receptor gating or Ca2+ permeability. 相似文献
5.
Abstract Resting cells of the fission yeast Schizosaccharomyces pombe , suspended in buffer with glucose, responded to the addition of asparagine by increasing trehalase activity. This response was preceded by a peak in cAMP concentration. The addition of the nitrogen source to resting cells, devoid of the catalytic subunit of cAMP-dependent protein kinase, produced the transient increase in cAMP but did not promote any change in trehalase activity. In the budding yeast Pachysolen iannophilus , the activation of trehalase by nitrogen source was also accompanied by a sharp peak in cAMP. These results suggest that in the two yeasts cAMP acts as a second messenger in the transduction of the nitrogen-source-induced signal causing the activation of trehalase. 相似文献
6.
环腺苷酸(cAMP)可在神经传递物刺激腺苷酸环化酶的作用下产生,而坏腺苷酸又可促成神经传递物的产生.用溴氰菊酯(deltamethrin)处理家蝇后,发现酪胺大量增加,主要由于酪氨酸脱羧酶受到诱导、活性增高所致.处理后一小时,cAMP也有增加,并与酶活性的增加相平行,但酪氨酸脱羧酶活性增高的曲线与cAMP量增加的曲线,实际上并不平行,因酪氨酸脱羧酶的活性是先增加,然后下降,而cAMP的量则是在开始时有一个小的下降,接着一直上升,而此时酶的诱导已下降,cAMP含量在诱导开始时出现下降的原因尚不明,可能与环鸟苷酸(cGMP)有关.但随后的上升显然是由于酪胺或章鱼胺的增加所造成.目前已证实,酪胺可经β-羟化作用形成章鱼胺,后者再刺激章鱼胺受体,而使腺苷酸环化酶活化,产生大量的cAMP.酪胺本身也可能就是章鱼胺受体的激活剂. 相似文献
7.
大肠杆菌 O55B5内毒素在体外可抑制人血小板自发性聚集,并使血小板内 cAMP、钙调素明显增高,但对肾上腺素诱发的血小板聚集无作用,也不能引起血小板致密颗粒和α-颗粒的释放。此外还观察到内毒素组无血小板上清液中5-HT 含量减少。 相似文献
8.
The effects of , , and receptor-agonists on forskolin stimulated cyclic adenosine-3, 5-monophosphate (cAMP) formation were examined in astroglial enriched primary cultures from the cerebral cortex of newborn rats. Intracellular cAMP accumulation was quantified by radioimmunoassay. Morphine was used as a -receptor agonist, D-Ala-D-Leu-Enkephalin (DADLE) as a -receptor agonist and dynorphine 1–13 (Dyn) as a -receptor agonist. Basal cAMP levels were unaffected by either the opiate agonists or the antagonists used. In the presence of the cAMP stimulator forskolin, morphine had no significant effect on the cytoplasmic cAMP levels. DADLE caused a dose related inhibition of the forskolin stimulated cAMP accumulation. The effects of this receptor stimulation was blocked with the selective antagonist ICI 174.864. In the presence of Dyn, the forskolin stimulated cAMP accumulation was inhibited in a dose related manner. This receptor stimulation was blocked with the selective antagonist MR 2266. Co-administration of DADLE and Dyn resulted in a non additive inhibition of the forskolin stimulated accumulation of cAMP. These findings indicate that astroglial enriched cultures from the cerebral cortex of rats express and -receptors co-localized ont he same population of cells, and that these receptors are inhibitory coupled to adenylate cyclase. 相似文献
9.
The adenylyl cyclase system of the yeast Saccharomyces cerevisiae contains the CYR1 polypeptide, responsible for catalyzing formation of cAMP from ATP, and two RAS polypeptides, responsible for stimulation of cAMP synthesis by guanine nucleotides. We have obtained rabbit antibodies that recognize the CYR1 protein. Antibodies were raised against synthetic oligopeptides and against a recombinant beta-galactosidase/CYR1 fusion protein. These antibodies have allowed the identification of the CYR1 gene product as a 205 kDa protein. Treatment with trypsin (2 micrograms/ml) reduced the size of the CYR1 protein from 205 to 155 kDa and produced an activated enzyme which no longer responded to guanine nucleotides. This result is consistent with a model in which adenylyl cyclase activity is regulated by an inhibitory domain near the amino-terminus of the CYR1 protein. This model is further supported by the finding that adenylyl cyclase activity is also markedly elevated and unresponsive to guanine nucleotides in mutant yeast strains that express only the carboxy-terminal half of the CYR1 protein. Treatment with high trypsin concentrations (greater than 10 micrograms/ml) caused release of adenylyl cyclase activity from the membrane. Comparison of immunoreactive CYR1 fragments released by trypsin and membrane bound genetically altered proteins suggests that the CYR1 protein is attached to the membrane via a separate trypsin sensitive anchoring protein rather than via a membrane anchoring domain. 相似文献
10.
Summary In view of the presumed involvement of gap junctions in the coordination of metabolic activities, the influence of cAMP as a regulatory signal of cell metabolism on gap junctions of hepatocytes has been examined. Male rats received two intraperitoneal doses of 10 mg dibutyryl cAMP/100 g body weight with a time interval of 2.5 h and were decapitated 2.5 h later. After this 5-h interval, analysis of freeze-fracture replicas of fixed liver tissue revealed an increase in the mean (± SEM) gap-junctional membrane portion on the lateral hepatocyte membranes from 0.049 + 0.003 (n = 66) in controls to 0.061 ± 0.003 (n = 70) in treated rats, while the configuration of the connexons appeared unaltered. This effect could not be reinforced by prior administration of aminophylline: the relative gapjunctional area is similarly extended from 0.054 ± 0.003 (n = 126) in the control group to 0.065 ± 0.004 (n = 105) in the experimental animals. Probing for the time course of the junctional response, a group of rats was sacrificed 3 h after the onset of treatment. Already within this time, the gapjunctional area is augmented from 0.042 ± 0.004 (n = 63) in the concurrent controls to 0.069 ± 0.006 (n = 42) in the treated rats. These statistically significant increases in area may suggest a stimulating effect of cAMP on gap junctions of hepatocytes in vivo.This investigation was supported by grant No. 3.0059.81 (to D.W.S.) from the Fund for Medical Scientific Research (Belgium) 相似文献