全文获取类型
收费全文 | 964篇 |
免费 | 28篇 |
国内免费 | 28篇 |
出版年
2023年 | 3篇 |
2022年 | 9篇 |
2021年 | 7篇 |
2020年 | 11篇 |
2019年 | 30篇 |
2018年 | 16篇 |
2017年 | 17篇 |
2016年 | 23篇 |
2015年 | 16篇 |
2014年 | 34篇 |
2013年 | 64篇 |
2012年 | 15篇 |
2011年 | 66篇 |
2010年 | 17篇 |
2009年 | 41篇 |
2008年 | 51篇 |
2007年 | 47篇 |
2006年 | 38篇 |
2005年 | 32篇 |
2004年 | 46篇 |
2003年 | 33篇 |
2002年 | 29篇 |
2001年 | 22篇 |
2000年 | 22篇 |
1999年 | 26篇 |
1998年 | 33篇 |
1997年 | 27篇 |
1996年 | 29篇 |
1995年 | 18篇 |
1994年 | 16篇 |
1993年 | 17篇 |
1992年 | 13篇 |
1991年 | 14篇 |
1990年 | 14篇 |
1989年 | 21篇 |
1988年 | 9篇 |
1987年 | 17篇 |
1986年 | 8篇 |
1985年 | 12篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 10篇 |
1978年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1969年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有1020条查询结果,搜索用时 31 毫秒
11.
E. R. S. Roldan S. Shibata R. Yanagimachi 《Molecular reproduction and development》1986,13(4):281-292
The effects of Ca2+ channel antagonists on the motility and acrosome reaction of guinea pig spermatozoa were examined by incubating the spermatozoa continuously in Ca2+-containing capacitating media with 10?6 M to 10?4 M antagonist. Antagonists tested were four voltage-gated Ca2+ channel antagonists (verapamil, nifedipine, nimodipine, and FR–34235) and two ligand-gated channel antagonists (NaNO2 and Na-nitroprusside). None of these antagonists could block the acrosome reaction. Instead, three antagonists (verapamil, nimodipine, and FR-34235, each at 10?4 M) accelerated the onset of the acrosome reaction with a subsequent decrease in sperm motility. Nifedipine and Na-nitroprusside at the same concentration caused a complete loss of sperm motility by 4 hr of incubation with no substantial effect on the rate of acrosome reaction. The detrimental effect of antagonists on the motility of spermatozoa appears to be due to a direct, Ca2+-independent, membrane-perturbing action of the reagents. The acrosome reaction was not inhibited when guinea pig spermatozoa were precapacitated in Ca2+-free medium (with a low concentration of lysolecithin) in the continuous presence of antagonists. An acceleration of the onset of the acrosome reaction by verapamil (10?4 M) was also demonstrated in the golden hamster. These results may be interpreted as indicating that the entry of extracellular Ca2+ into spermatozoa, which triggers the acrosome reaction of guinea pig and hamster spermatozoa, is not mediated by Ca2+ channels. This is in marked contrast with the case reported in invertebrate spermatozoa. Possible mechanisms by which some of the antagonists stimulate the acrosome reaction and affect the motility of mammalian spermatozoa are discussed. 相似文献
12.
Summary In the isolated bullfrog cornea, three calcium channel antagonists had dose-dependent inhibitory effects on the Cl-originated short-circuit current (SCC). Their order of decreasing potency was bepridil, verapamil and diltiazem. One millimolar diltiazem inhibited the SCC by 98% and subsequent incubation with the calcium ionophore A23187 had no restorative effect. Increasing the bathing solution Ca concentration from 0.05 to 15mm, however, decreased diltiazem's inhibitory efficacy. This antagonist depolarized the intracellular potential differenceV
m
from –54 to –18 mV (tear: reference) and the voltage divider ratioFR
0 decreased from 0.58 to 0.30, suggesting an increase in basolateral membrane electrical resistance. Additional indication of a basolateral membrane effect by the drug was that preincubation with 105
m amphotericin B in Cl-free Ringer's did not eliminate the inhibitory effect of the drug on the Na- and K-elicited SCC. In the absence of amphotericin B in Cl-free Ringer's (SCC=0), 1 ×103
m diltiazem depolarized theV
m
from –78 to –9 mV suggesting that the increase in basolateral membrane resistance was due to K channel blockade. Diltiazem (1×103
m) significantly decreased cyclic AMP content; however, isoproterenol in the presence of the drug increased cyclic AMP fourfold without having any restorative effect on the inhibited SCC. Therefore, the inhibition of the Cl-originated SCC resulting from an increase in basolateral membrane K resistance is not caused by a decline in cyclic AMP content. In plasma membrane-enriched fractions prepared from broken cell preparations of bovine corneal epithelium, 1×103
m diltiazem had no inhibitory effects on either Na,K-ATPase or Ca,Mg-ATPase activities. These latter effects further point to the selectivity of diltiazem as an inhibitor of K-channel activity, but do not preclude a Ca-channel blocker effect by the drug in the micromolar range. 相似文献
13.
Competitive antagonists of bradykinin 总被引:35,自引:0,他引:35
The first sequence-related competitive inhibitors of the classic kinin in vitro (rat uterus guinea pig ileum) and in vivo (rat blood pressure) assays have been developed. Replacement of the proline residue at position 7 of bradykinin (BK) with a D-phenylalanine residue is the key modification which converts BK agonists into antagonists. [D-Phe7]-BK exhibits moderate (pA2 = 5.0) inhibition of BK activity on the guinea pig ileum but possesses weak BK-like myotropic activity on the isolated rat uterus and 2-4% of BK depressor potency in the rat blood pressure assay. The additional replacement of the phenylalanine residues at positions 5 and 8 of [D-Phe7]-BK with the isosteric beta-(2-thienyl)-alanine residue produces a potent antagonist of BK activity on the uterus (pA2 = 6.4), ileum (pA2 = 6.3), and in the rat blood pressure assay. The antagonism of BK action on smooth muscle is specific for kinins (BK, kallidin, Met-Lys-BK), but neither inhibitor antagonizes the smooth muscle activity of angiotensin or substance P. Inhibition is competitive and fully reversible. 相似文献
14.
BAY K 8644, a 1,4-Dihydropyridine Ca2+ Channel Activator: Dissociation of Binding and Functional Effects in Brain Synaptosomes 总被引:6,自引:0,他引:6
K+-stimulated 45Ca2+ uptake into rat brain and guinea pig cerebral cortex synaptosomes was measured at 10 s and 90 s at K+ concentrations of 5-75 mM. Net increases in 45Ca2+ uptake were observed in rat and guinea pig brain synaptosomes. 45Ca2+ uptake under resting or depolarizing conditions was not increased by the 1,4-dihydropyridine BAY K 8644, which has been shown to activate Ca2+ channels in smooth and cardiac muscle. High-affinity [3H]nitrendipine binding in guinea pig synaptosomes (KD = 1.2 X 10(-10) M, Bmax = 0.56 pmol mg-1 protein) was competitively displaced with high affinity (IC50 2.3 X 10(-9) M) by BAY K 8644. Thus high-affinity Ca2+ channel antagonist and activator binding sites exist in synaptosome preparations, but their relationship to functional Ca2+ channels is not clear. 相似文献
15.
Synopsis Black surfperch, Embiotoca jacksoni, and striped surfperch, Embiotoca lateralis, coexisted along steep sloping rocky habitats at Santa Cruz Island, California. The range of depths occupied (to 15 m) was characterized by a strong gradient in abundance of prey and a changing mosaic of substrate types from which surfperch harvested food. Availability of prey and diversity of benthic substrates were greatest in shallowest areas and both declined with increasing depth. Individuals of both surfperch species were residential within a narrow range of depths, with the result that different segments of their populations were consistently exposed to different foraging environments. These two phenomena (residential behavior combined with a gradient in availability of resources) resulted in variation in foraging behaviors and diets among individuals that resided at different depths. The pattern of within-population variation differed between the surfperch species. Black surfperch individuals achieved similar taxonomic diets and expended similar foraging effort at all depths, but deep-water foragers captured much less prey biomass per unit effort. The taxonomic composition of striped surfperch diets differed among depths, and although similar amounts of prey biomass were captured everywhere, individuals in deep areas expended much greater effort to obtain that level of food return. For both species, habitat profitability (food return to foraging effort) declined with depth. The difference in habitat profitability appeared to influence fitness components of both surfperches. Individuals occupying deep habitats were about 5% shorter in standard length than conspecifics of the same chronological age living in shallow areas; the disparity in body size resulted in an estimated difference in clutch size of 10–18%. 相似文献
16.
Effect of Some Calcium Antagonists on Muscarinic Receptor-Mediated Cyclic GMP Formation 总被引:3,自引:2,他引:1
Several calcium antagonists were screened for their effect on muscarinic acetylcholine receptor-mediated cyclic GMP formation in murine neuroblastoma cells (clone N1E-115). Mn2+, Ni2+, and verapamil rapidly antagonized the response noncompetitively, with the following order of potency: verapamil greater than Mn2+ greater than Ni2+. The effects of Mn2+ and Ni2+, but not those of verapamil, were largely reversed by increasing extracellular calcium concentration. Additional effects of these agents included displacement of [3H]quinuclidinyl benzilate binding by verapamil and elevation of cyclic GMP levels by Mn2+ and Ni2+ in the absence of agonists. These results are in support of the hypothesis that receptor-mediated cyclic GMP formation by these cells is dependent upon entry of calcium into the cell and demonstrate the complexity of the effects of calcium antagonists. 相似文献
17.
Apple trees ( Malus pumila Mill . var. domestica Fuji/ Malus prunifolia rootstock) showed a high susceptibility to bitter pit when supplyed with ammonium salt instead of nitrate (control) in the nutrient solution. When apple fruit was affected by bitter pit, a lower calcium as well as a higher nitrogen and ammonium-nitrogen contents was observed in the fruit flesh near the calyx end. The activity of the mitochondrial Ca2+ -uptake of the fruit flesh near the calyx end was higher when the tree was grown with ammonium salt than when grown with nitrate. Both the activities of succinate: cytochrome c oxidoreductase and the mitochondrial Ca2+ -uptake per g of tissue were higher in affected fruit than in healthy fruit. Each of chlorpromazine, N-(6-aminohexyl)-5-chloro-l-napthalenesulfonamide (W-7) and N-(6-aminohexyl)-l-naphthalenesulfonamide (W-5), calmodulin antagonists, was infiltrated into the fruit for 20 min under reduced pressure (about 1 × 104 Pa). Few days later, numerous bitter pit-like spots were observed in both fruit treated with W-7 and chlorpromazine, while only a few spots were observed after the infiltration with W-5, a less potent calmodulin antagonist. A possible mechanism for the occurrence of bitter pit is discussed. 相似文献
18.
JAYNE A. BUFFEY SARAH E. HILL STANLEY S. BLEEHEN ANTHONY J. THODY S. MAC NEIL 《Pigment cell & melanoma research》1991,4(3):112-119
Previous work from our laboratory has shown that both cyclic AMP and calcium/calmodulin appear to be involved in the regulation of melanogenesis in murine B16 melanoma cells. In these cells as in murine Cloudman S91 cells, melanogenic responsiveness to melanocyte-stimulating hormone (MSH) varies with cell density in culture. Our objective in this study was to learn more about the intracellular systems involved in the control of melanogenesis, particularly the role played by calcium. The melanogenic response to αMSH was compared to the response to drugs affecting intracellular free calcium and calmodulin over a range of cell densities in B16F1 cells. αMSH-stimulated melanin production was extremely density-dependent but αMSH-stimulated cyclic AMP production was independent of cell density. The melanogenic response to agents that increased intracellular calcium (A23187) or inhibited intracellular calmodulin varied with cell density. A drug (TMB8) that lowered intracellular free calcium, however, increased melanogenesis independently of cell density. At high cell density it was found that an elevation in calcium decreased melanogenesis, whereas agents that reduced calcium or inhibited calmodulin activity increased melanogenesis. At low cell density, however, the inhibitory response to A23187 was lost and in some experiments even stimulated melanogenesis. These data suggest that the calcium/calmodulin signalling system has an inhibitory influence on melanogenesis, and its expression, which depends upon cell density, may also modulate the response to stimulatory agents such as αMSH. 相似文献
19.
20.
Ryozo Oishi Naoto Adachi Keishi Okada Nobuyuki Muroi Kiyomi Saeki 《Journal of neurochemistry》1990,55(6):1899-1904
To clarify the regulation of central histaminergic (HAergic) activity by cholinergic receptors, the effects of drugs that stimulate the cholinergic system on brain histamine (HA) turnover were examined, in vivo, in mice and rats. The HA turnover was estimated from the accumulation of tele-methylhistamine (t-MH) during the 90-min period after administration of pargyline (65 mg/kg, i.p.). In the whole brain of mice, oxotremorine, at doses higher than 0.05 mg/kg, s.c., significantly inhibited the HA turnover, this effect being completely antagonized by atropine but not by methylatropine. A large dose of nicotine (10 mg/kg, s.c.) also significantly inhibited the HA turnover. This inhibitory effect was antagonized by mecamylamine but not by atropine or hexamethonium. A cholinesterase inhibitor, physostigmine, at doses higher than 0.1 mg/kg, s.c., significantly inhibited the HA turnover. This effect was antagonized by atropine but not at all by mecamylamine. None of these cholinergic antagonists used affected the steady-state t-MH level or HA turnover by themselves. In the rat brain, physostigmine (0.1 and 0.3 mg/kg, s.c.) also decreased the HA turnover. This inhibitory effect of physostigmine was especially marked in the striatum and cerebral cortex where muscarinic receptors are present in high density. Oxotremorine (0.2 mg/kg, s.c.) and nicotine (1 mg/kg, s.c.) also decreased the HA turnover in the rat brain. However, these effects showed no marked regional differences. These results suggest that the stimulation of central muscarinic receptors potently inhibits the HAergic activity in the brain and that strong stimulation of central nicotinic receptors can also induce a similar effect. 相似文献