全文获取类型
收费全文 | 1984篇 |
免费 | 8篇 |
国内免费 | 17篇 |
出版年
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 9篇 |
2019年 | 19篇 |
2018年 | 30篇 |
2017年 | 13篇 |
2016年 | 15篇 |
2015年 | 36篇 |
2014年 | 74篇 |
2013年 | 85篇 |
2012年 | 66篇 |
2011年 | 133篇 |
2010年 | 73篇 |
2009年 | 56篇 |
2008年 | 58篇 |
2007年 | 66篇 |
2006年 | 54篇 |
2005年 | 54篇 |
2004年 | 49篇 |
2003年 | 49篇 |
2002年 | 36篇 |
2001年 | 13篇 |
2000年 | 35篇 |
1999年 | 38篇 |
1998年 | 53篇 |
1997年 | 67篇 |
1996年 | 55篇 |
1995年 | 64篇 |
1994年 | 47篇 |
1993年 | 39篇 |
1992年 | 46篇 |
1991年 | 52篇 |
1990年 | 42篇 |
1989年 | 51篇 |
1988年 | 32篇 |
1987年 | 40篇 |
1986年 | 35篇 |
1985年 | 31篇 |
1984年 | 46篇 |
1983年 | 37篇 |
1982年 | 40篇 |
1981年 | 31篇 |
1980年 | 41篇 |
1979年 | 51篇 |
1978年 | 5篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1975年 | 6篇 |
1974年 | 2篇 |
1973年 | 6篇 |
排序方式: 共有2009条查询结果,搜索用时 20 毫秒
61.
Abstract: Histamine (HA) potently stimulated cyclic AMP accumulation in intact pineal glands taken from light-exposed chicks. The action of HA was stronger in the presence of forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). The effect of HA was mimicked by HA H1- and H2-receptor-selective agonists in the following order of potency: HA > 4-methylhistamine (H2) > 2-methylhistamine (H1) > 2-thiazolylethylamine (H1) ≫ dimaprit (H2). The HA H3-receptor-selective agonist (R)α-methylhistamine was poorly active. The effect of HA was antagonized by selective H2-receptor blockers (tiotidine > oxmetidine > cimetidine = ranitidine) and was not significantly affected by the selective H1- and H3-receptor blockers mepyramine and thioperamide. A detailed analysis of an antagonistic action of ranitidine (versus HA) revealed a noncompetitive mode of action of the H2 blocker. The stimulatory action of the H1 agonist 2-thiazolylethylamine (both under basal conditions and in the presence of forskolin or IBMX) was not significantly influenced by three H1-receptor-selective blockers (mepyramine, triprolidine, and diphenhydramine), but it was totally counteracted by ranitidine. Using accepted selective agonists and antagonists of the HA H1, H2, and H3 receptor we were unable to identify clearly the receptor subtype mediating the HA action on the cyclic AMP-generating system of the chick pineal. It is suggested that the receptor under consideration may represent either an H2-like (in terms of mammalian criteria) or avian-specific HA receptor. The data suggest that HA may be considered a modulator of the pineal activity in chicks. 相似文献
62.
Inhibition of Dopamine Agonist-Induced Phosphoinositide Hydrolysis by Concomitant Stimulation of Cyclic AMP Formation in Brain Slices 总被引:4,自引:0,他引:4
Abstract: We examined the effects of cyclic AMP on dopamine receptor-coupled activation of phosphoinositide hydrolysis in rat striatal slices. Forskolin, dibutyryl cyclic AMP, and the protein kinase A activator Sp -cyclic adenosine monophosphothioate ( Sp -cAMPS) significantly inhibited inositol phosphate formation stimulated by the dopamine D1 receptor agonist SKF 38393. Conversely, the protein kinase A antagonist Rp -cyclic adenosine monophosphothioate ( Rp -cAMPS) dose-dependently potentiated the SKF 38393 effect. In the presence of 200 µ M Rp -cAMPS, the dose-response curves of the dopamine D1 receptor agonists SKF 38393 and fenoldopam were shifted to the left and maximal agonist responses were markedly increased. The agonist EC50 values, however, were not significantly altered by protein kinase A inhibition. Neither Sp -cAMPS nor Rp -cAMPS significantly affected basal inositol phosphate accumulation. These findings demonstrate that dopaminergic stimulation of phosphoinositide hydrolysis is inhibited by elevations in intracellular cyclic AMP. Dopamine receptor agonists that stimulate adenylyl cyclase could suppress their activation of phosphoinositide hydrolysis by concomitantly stimulating the formation of cyclic AMP in striatal tissue. The interaction between dopamine D1 receptor-stimulated elevations in cyclic AMP and dopaminergic stimulation of inositol phosphate formation suggests a cellular colocalization of these dopamine-coupled transduction pathways in at least some cells of the rat striatum. 相似文献
63.
64.
Félix Hernàndez Stephen P. H. Alexander David A. Kendall 《Journal of neurochemistry》1994,62(6):2212-2218
Abstract: In this study, the interaction between 3′,5′-cyclic adenosine monophosphate (cAMP) and 3′,5′-cyclic guanosine monophosphate (cGMP) in [3H]adenine-or [3H]-guanine-prelabelled adult guinea-pig cerebellar slices was investigated. Basal levels of [3H]cGMP were enhanced by forskolin, although no plateau was reached over the concentration range tested (0.1-100 μM). However, forskolin elicited a concentration-dependent, saturable potentiation of sodium nitroprusside (SNP)-stimulated [3H]cGMP accumulation (forskolin EC50 value of 0.98 β 0.23 μM; 10 μM forskolin produced a 1.8 β 0.3-fold potentiation of the SNP response at 2.5 min). The forskolin potentiation was observed at all concentrations of SNP tested (0.001-10 mM). forskolin also elicited a large stimulation of [3H]-cAMP in [3H]adenine-prelabelled guinea-pig cerebellar slices; however, 1,9-dideoxyforskolin failed to elicit either a [3H]cAMP response or a potentiation of the SNP-induced [3H]cGMP response at concentrations up to 100 μM. Pretreatment with oxyhaemoglobin (50 μM) inhibited the response to SNP (1 mM) and forskolin (10 μM), as well as the response evoked by the combination of SNP and forskolih. AG-Nitro-l -arginine (100 μM) inhibited the response to forskolin alone, but did not change the response to SNP or the potentiation induced by forskolin on SNP-induced [3H]cGMP levels. The protein kinase inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7; 100 μM), staurosporine (10 μM), polymyxin B (100 μM), and Ro 31-8220 (10 μM) had no effect on the [3H]cGMP response to either SNP or the combination of SNP plus forskolin. N6,2′-Dibutyryl cAMP, at concentrations up to 10 mM, was also without effect on [3H]cGMP levels induced by SNP. 3-lso-butyl-1-methylxanthine reproduced the effect of forskolin on SNP-induced [3H]cGMP levels, but a less-than-additive effect was observed when the response to SNP was studied in the presence of forskolin and 3-isobutyl-1-methylxanthine. Taken together, these results infer that crosstalk between cyclic nucleotides takes place in guinea-pig cerebellar slices, and that cAMP may regulate cGMP-mediated responses in this tissue. 相似文献
65.
Stefan Boehm Sigismund Huck Gabriele Koth Helmut Drobny Ernst Agneter Ernst A. Singer 《Journal of neurochemistry》1994,63(1):146-154
Abstract: This study explores the role of cyclic AMP in electrically evoked [3H]noradrenaline release and in the α2-adrenergic modulation of this release in chick sympathetic neurons. Along with an increase in stimulation-evoked tritium overflow, applications of forskolin enhanced the formation of intracellular cyclic AMP. Both effects of forskolin were potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The forskolin-induced increase in overflow was abolished by the Rp-diastereomer of cyclic AMP-thioate, an antagonist at cyclic AMP-dependent protein kinases, and 1,9-dideoxy-forskolin, an inactive analogue at adenylyl cyclase, had no effect on the evoked overflow. A 24-h pretreatment with either cholera toxin or forskolin reduced the subsequent forskolin-induced accumulation of cyclic AMP and inhibited the stimulation-evoked release. Basal cyclic AMP production, however, remained unaltered after forskolin treatment and was enhanced after 24 h of cholera toxin exposure. The α2-adrenergic agonist bromoxidine did not affect the formation of cyclic AMP stimulated by forskolin but reduced electrically evoked release. However, effects of bromoxidine on 3H overflow were attenuated by forskolin as well as by 8-bromo-cyclic AMP. Effects of bromoxidine on [3H]noradrenaline release were paralleled by an inhibition of voltage-activated Ca2+ currents, primarily through a delayed time course of current activation. This effect was abolished when either forskolin or 8-bromo-cyclic AMP was included in the pipette solution. Both substances, however, failed to affect Ca2+ currents in the absence of bromoxidine. These results suggest that the signaling cascade of the α2-adrenergic inhibition of noradrenaline release involves voltage-activated Ca2+ channels but not cyclic AMP. Elevated levels of cyclic AMP, however, antagonize this α2-adrenergic reduction, apparently through a disinhibition of Ca2+ channels. 相似文献
66.
Stimulation of the Cyclic GMP Pathway by NO Induces Expression of the Immediate Early Genes c-fos and junB in PC12 Cells 总被引:7,自引:2,他引:5
Christelle Haby Fabrice Lisovoski Dominique Aunis Jean Zwiller 《Journal of neurochemistry》1994,62(2):496-501
Abstract: Stimulation of several second messenger pathways induces the expression of immediate early genes such as c- fos , c- jun , junB , and junD , but little is known about their induction via the stimulation of the cyclic GMP pathway. Here we looked at the expression of early genes in pheochromocytoma PC12 cells after activation of cytosolic guanylate cyclase by sodium nitroprusside. This compound spontaneously releases NO, a molecule known to be involved in cell communication. We found that expression of c- fos and junB but not of c- jun or junD is increased upon activation of cyclic GMP pathway. c- fos mRNA expression was the most activated (fourfold at 30 min), whereas junB response was more modest (2.2-fold activation at 60 min). Nuclear extracts of stimulated cells show increased binding capacity to the AP1 binding site consistent with the dose-response curve. The activating effect of nitroprusside could be reproduced by dipyridamole, a selective cyclic GMP phosphodiesterase inhibitor and by 8- p -chlorophenylthio-cyclic GMP, a permeant selective cyclic GMP-dependent protein kinase activator, and abolished by KT5823, an inhibitor of that kinase. The results show that NO promotes early gene activation and AP1 binding enhancement through the stimulation of the cyclic GMP pathway. 相似文献
67.
68.
Yoichi Tamai Hisako Kojima Shintaro Saito† Kikue Uchida Rie Kitajima Hiroshi Komatsu Tsuneo Moriya‡ 《Journal of neurochemistry》1993,60(5):1854-1863
Abstract: The metamorphic changes in levels of glycolipids and myelin proteins and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) in the brains of bullfrog tadpoles, adult frogs, and axolotls were investigated, with particular emphasis on myelin maturation. The concentrations of cerebroside. sulfatide, and galactosyldiacylglycerol gradually increased from the onset of prometamorphosis throughout the active metamorphic period and then greatly increased after metamorphosis was completed. The ratio of glucocerebroside to galactocerebroside increased greatly in the prometamorphic period and then rapidly decreased to the frog level during the climax period. The fatty acid compositions of cerebroside and sulfatide showed a developmental change, with 24:1 being more predominant in the later metamorphic stage. The proportion of hydroxy fatty acids increased up to the onset of the prometamorphic stage and thereafter remained constant at ∼ 50% of the total. The CNP activity remained unchanged throughout metamorphosis at 60% that in frog myelin and increased in the adult frog. The composition of tadpole myelin proteins remained constant during metamorphosis, with large basic protein being the most abundant, and in the frog, proteolipid protein and large basic protein were present in comparable amounts. The two adult forms of axolotl, i.e., the neotenous and metamorphosed forms, exhibited almost identical myelin constituents, and CNP activity in the neotenous form amounted to one-fifth that in the bullfrog. These results indicate that active biosynthesis of myelin marker components occurs as metamorphosis proceeds, but more pronounced changes of myelin components occur after metamorphosis is completed. 相似文献
69.
Abstract: Cyclic GMP (cGMP) formation in rat pinealocytes is regulated through a synergistic dual receptor mechanism involving β-and α1 -adrenergic receptors. The effects of N -monomethyl- l -arginine (NMMA), which inhibits nitric oxide (NO) synthase and NO-mediated activation of cytosolic guanylate cyclase, and methylene blue (MB), which inhibits cytosolic guanylate cyclase, were investigated in an attempt to understand the role of NO in adrenergic cGMP formation. Both NMMA and MB inhibited β-adrenergic stimulation of cGMP formation as well as α1 -adrenergic potentiation of β-adrenergic stimulation of cGMP formation, whereas they had no effect in unstimulated pinealocytes. The inhibitory action of NMMA was antagonized by addition of l -arginine. On the basis of these findings it can be concluded that the adrenergic stimulation of cGMP formation involves NO synthesis followed by activation of cytosolic guanylate cyclase. 相似文献
70.