全文获取类型
收费全文 | 24775篇 |
免费 | 2184篇 |
国内免费 | 1689篇 |
专业分类
28648篇 |
出版年
2024年 | 45篇 |
2023年 | 211篇 |
2022年 | 442篇 |
2021年 | 722篇 |
2020年 | 575篇 |
2019年 | 746篇 |
2018年 | 805篇 |
2017年 | 688篇 |
2016年 | 971篇 |
2015年 | 1473篇 |
2014年 | 1656篇 |
2013年 | 1866篇 |
2012年 | 2192篇 |
2011年 | 2039篇 |
2010年 | 1385篇 |
2009年 | 1179篇 |
2008年 | 1527篇 |
2007年 | 1386篇 |
2006年 | 1216篇 |
2005年 | 1132篇 |
2004年 | 1061篇 |
2003年 | 977篇 |
2002年 | 859篇 |
2001年 | 447篇 |
2000年 | 371篇 |
1999年 | 323篇 |
1998年 | 244篇 |
1997年 | 196篇 |
1996年 | 154篇 |
1995年 | 138篇 |
1994年 | 99篇 |
1993年 | 85篇 |
1992年 | 129篇 |
1991年 | 110篇 |
1990年 | 101篇 |
1989年 | 107篇 |
1988年 | 99篇 |
1987年 | 86篇 |
1986年 | 73篇 |
1985年 | 87篇 |
1984年 | 60篇 |
1983年 | 53篇 |
1982年 | 43篇 |
1980年 | 35篇 |
1979年 | 55篇 |
1978年 | 47篇 |
1977年 | 32篇 |
1976年 | 46篇 |
1975年 | 36篇 |
1974年 | 34篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
Abstract: The α subunit of Gz (αz) harbors two N-terminal serine residues (at positions 16 and 27) that serve as protein kinase C-mediated phosphorylation sites. The cognate residues in the α subunit of Gt1 provide binding surfaces for the β1 subunit. We used three serine-to-alanine mutants of αz to investigate the functional importance of the two N-terminal serine residues. Wild-type or mutant αz was transiently coexpressed with different receptors and adenylyl cyclase isozymes in human embryonic kidney 293 cells, and agonist-dependent regulation of cyclic AMP accumulation was examined in a setting where all endogenous α subunits of Gi were inactivated by pertussis toxin. Replacement of one or both serine residues by alanine did not alter the ability of αz to interact with δ-opioid, dopamine D2, or adenosine A1 receptors. Its capacity to inhibit endogenous and type VI adenylyl cyclases was also unaffected. Functional release of βγ subunits from the mutant αz subunits was not impaired because they transduced βγ-mediated stimulation of type II adenylyl cyclase. Constitutively active mutants of all four αz subunits were constructed by the introduction of a Q205L mutation. The activated mutants showed differential abilities to inhibit human choriogonadotropin-mediated cyclic AMP accumulation in luteinizing hormone receptor-transfected cells. Loss of both serine residues, but not either one alone, impaired the receptor-independent inhibition of adenylyl cyclase by the GTPase-deficient mutant. Thus, replacement of the amino-terminal serine residues of αz has no apparent effect on receptor-mediated responses, but these serine residues may be essential for ensuring transition of αz into the active conformation. 相似文献
102.
The purpose of this investigation was to determine whether Madurella mycetomatis, the most frequent agent of eumycotic mycetomas, produces siderophores and synthesizes new outer membrane proteins under iron-starvation conditions. Siderophore production, only of the hydroxamate type, was demonstrated in all nine strains tested. It was regulated by extracellular iron concentrations. Under iron-restricted conditions, M. mycetomatis expressed various outer membrane iron-regulated proteins, particularly of 24-kilodalton, that may participate in iron metabolism. 相似文献
103.
104.
We examined the effect of prostaglandin E2 (PGE2), in the presence or absence of cortisol, on bone formation in 21-day fetal rat calvaria maintained in organ culture for 24 to 96 h. [3H]Thymidine and [3H] proline incorporation were used to assess DNA and collagen synthesis, respectively. Changes in dry weight and DNA content were assessed after 96 h.PGE2 (10−7 M) stimulated both DNA and collagen synthesis in calvaria. The effect on DNA synthesis was early (24 h), transient and limited to the periosteum. Collagen synthesis was stimulated at a later time (96 h), predominantly in the central bone. Cortisol (10−7 M) inhibited DNA and collagen synthesis. The addition of PGE2 reversed the inhibitory effects of cortisol on DNA synthesis and content and increased collage synthesis in central bone to levels above control untreated cultures.We conclude that PGE2 has stimulatory effects on bone formation and can reverse the inhibitory effects of cortisol. Hence the effects of cortisol may be mediated in part by their ability to reduce the endogenous production of prostaglandins. 相似文献
105.
106.
The histidine-binding protein J of Salmonella typhimurium binds L-histidine as a first step in the high-affinity active transport of this amino acid across the cytoplasmic membrane. High-resolution nuclear magnetic resonance spectroscopy has been used to monitor the conformation of histidine-binding protein J in the presence and absence of substrate. Evidence is presented to show that this binding protein undergoes a conformational change involving a substantial number of amino-acid residues (including tryptophans) in the presence of L-histidine and that this change is specific for L-histidine. In order to monitor the involvement of tryptophan residues in the substrate-induced conformational change, 5-fluorotryptophan has been incorporated biosynthetically into the histidine-binding protein J using a tryptophan autotroph of Salmonella typhimurium. There are no significant differences in the conformation and binding activity between the 5-fluorotryptophan-labeled and the normal histidine-binding protein J. Proton and fluorine-19 nuclear magnetic resonance studies of the 5-fluorotryptophan-labeled binding protein show that at least one (and possibly two) of the tryptophan residues undergo(es) a change toward a more hydrophobic environment in the presence of L-histidine. These observations are supported by fluorescence data and by differences in the reactivity of the tryptophan residues of this protein toward N-bromosuccinimide in the presence and absence of substrate. The present results are consistent with models for the action of periplasmic-binding proteins in shock-sensitive transport systems of gram-negative bacteria which require a substrate-induced conformational change prior to the energy-dependent translocation of substrates. 相似文献
107.
Dynamic light scattering has been used to study the temperature dependence of Ca2+-induced fusion of phosphatidylserine vesicles and mixed vesicles containing phosphatidylserine and different phosphatidylcholines. The final vesicle size after Ca2+ and EDTA incubation serves as a measure of the extent of fusion. With phosphatidylserine vesicles, the extent of fusion shows a sharp maximum at an incubation temperature which depends on the Ca2+ concentration between 0.8 and 2 mM. The shift in the fusion peak temperature with Ca2+ concentration is similar to the typical shift in the phase transition temperature with divalent cation concentration in acidic phospholipids. The results suggest a direct correlation between the fusion peak temperature and the phase transition temperature in the presence of Ca2+ prior to fusion. With mixed vesicles containing up to 33% of a phosphatidylcholine in at least 2 mM Ca2+, the extent of fusion as a function of incubation temperature also shows a maximum. The fusion peak temperature is essentially independent of the quantity and type of phosphatidylcholine and the Ca2+ concentration, and identical to that with pure phosphatidylserine in excess Ca2+. The results imply that Ca2+-induced molecular segregation occurs first, and fusion subsequently takes place between pure phosphatidylserine domains. 相似文献
108.
Summary A large pedigree with a satellited Yq chromosome is described, Q, C, and NOR banding were performed. Family C proband suffers from a Klinefelter syndrome. 相似文献
109.
Summary Hormone stimulated lipolysis of mouse and rabbit adipocytes as measured by both free fatty acid and glycerol release, is proportionally
elevated with increase in the adipocyte cAMP level up to 1 nmole/g. The correlation coefficients are 0.94 and 0.97 for FFA/cAMP
and glycerol/cAMP respectively. Increments in cAMP greater than 1 nmole/g show no correlation with increase in lipolysis.
The release of lipolytic products, glycerol and free fatty acids, from white adipocytes in response to ACTH, epinephrine or
morepinephrine was measured using radiochemical assays in short term incubation systems, with cAMP levels measured at the
same time and from the same cell sample. Under the conditions studied, epinephrine is a more effective lipolytic hormone than
ACTH in mouse adipocyte, and ACTH is more effective than epinephrine in rabbit adipocyte. The effect of catecholamines on
the rabbit adipocyte is not modified by phentolamine (10 μM), but it is potentiated by 1-methyl-3-isobutyl xanthine (0.1 mM).
The results suggest that cAMP mediates the action of these lipolytic hormones in white adipocytes of mouse and rabbit. 相似文献
110.
Rubratoxin B, a lactone-containing bisanhydride metabolite of certain toxigenic molds, inhibited (Na+-K+)-stimulated ATPase activity of mouse brain microsomes in a dose-dependent manner with an estimated IC50 of 6 x 10(-6) M. Hydrolysis of ATP was linear with time and enzyme concentration, with or without rubratoxin in reaction mixtures. Altered pH and activity curves for (Na+-K+)-ATPase demonstrated comparable inhibition by rubratoxin in buffered acidic, neutral, and alkaline pH ranges. Kinetic studies of cationic-substrate activation of (Na+-K+)-ATPase indicated classical competitive inhibition for Na+ and K+. Results also showed competitive inhibition for K+ activated p-nitrophenyl phosphatase as demonstrated by altered binding site parameters without change in the catalytic velocity of dephosphorylation of the enzyme . phosphoryl complex. Noncompetitive inhibition with regards to activation by ATP and p-nitrophenyl phosphate was indicated by altered Vmax values with no change in Km values. Inhibition was partially restored by repeated washings. Preincubation with sulfhydryl agents protected the enzyme from inhibition. Cumulative inhibition studies with rubratoxin and ouabain indicated possible interaction between the two inhibitors of (Na+-K+)-ATPase. Rubratoxin appeared to exert its effects on (Na+-K+)-ATPase by interacting at Na+ and K+ sites. 相似文献