全文获取类型
收费全文 | 1653篇 |
免费 | 97篇 |
国内免费 | 24篇 |
出版年
2024年 | 4篇 |
2023年 | 24篇 |
2022年 | 26篇 |
2021年 | 60篇 |
2020年 | 45篇 |
2019年 | 47篇 |
2018年 | 41篇 |
2017年 | 32篇 |
2016年 | 37篇 |
2015年 | 52篇 |
2014年 | 63篇 |
2013年 | 99篇 |
2012年 | 61篇 |
2011年 | 68篇 |
2010年 | 73篇 |
2009年 | 62篇 |
2008年 | 88篇 |
2007年 | 76篇 |
2006年 | 71篇 |
2005年 | 66篇 |
2004年 | 76篇 |
2003年 | 75篇 |
2002年 | 66篇 |
2001年 | 65篇 |
2000年 | 22篇 |
1999年 | 25篇 |
1998年 | 21篇 |
1997年 | 20篇 |
1996年 | 21篇 |
1995年 | 35篇 |
1994年 | 25篇 |
1993年 | 31篇 |
1992年 | 23篇 |
1991年 | 23篇 |
1990年 | 25篇 |
1989年 | 15篇 |
1988年 | 14篇 |
1987年 | 10篇 |
1986年 | 14篇 |
1985年 | 12篇 |
1984年 | 10篇 |
1983年 | 11篇 |
1982年 | 11篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1973年 | 1篇 |
排序方式: 共有1774条查询结果,搜索用时 468 毫秒
21.
In the present study, we have applied the brain microdialysis technique to investigate the effect of the stimulation of adenylate cyclase on the extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of freely moving rats. Infusion of 8-bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine, or forskolin produced a significant increase in the release of DA. The effect of 8-Br-cAMP was tetrodotoxin, Ca2+, and dose dependent and was saturable. 8-Br-cAMP also caused an increase in the output of DOPAC and HVA. No effects were seen on the output of 5-HIAA, except at the highest 8-Br-cAMP concentration studied. Infusion of 8-Br-cAMP (25 microM, 1.0 mM, and 3.3 mM) together with infusion of (-)-sulpiride (1 microM) or systemic administration of (+/-)-sulpiride (55 mumol/kg i.p.) produced an additive effect on the release of DA. Infusion or peripheral administration of (-)-N-0437 (1 microM or 1 mumol/kg) both decreased the 8-Br-cAMP-induced increase in the release of DA. These results demonstrate that cyclic AMP may stimulate the release of DA, but it is unlikely that this second messenger is linked to presynaptic D2 receptors controlling the release of DA. 相似文献
22.
Bernard J. Van Vliet Arie H. Mulder Anton N. M. Schoffelmeer 《Journal of neurochemistry》1990,55(4):1274-1280
The receptors mediating the inhibition of D1 dopamine receptor-stimulated adenylate cyclase by opioids were examined in primary cultures of rat neostriatal neurons. Adenylate cyclase activity was dose-dependently increased by the selective D1 dopamine receptor agonist SKF 38393 (EC50 = 0.05 microM). This stimulation was fully antagonized by the selective D1 dopamine receptor antagonist SCH 23390 (1 microM). SKF 38393 (1 microM)-stimulated adenylate cyclase activity was strongly reduced (by almost 60%) by the highly selective mu-agonist [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAGO; EC50 = 0.006 microM) and high concentrations of the selective delta-agonist [D-Ser2(O-tert-butyl), Leu5]-enkephalyl-Thr6 (DSTBU-LET; EC50 = 0.13 microM) but not by the selective delta-agonist [D-penicillamine2, D-penicillamine5]enkephalin (DPDPE). D1 dopamine receptor-stimulated adenylate cyclase activity was also slightly reduced (by approximately 20%) by high concentrations of the kappa-agonist U50,488 (EC50 = 0.63 microM). The inhibitory effects of submaximally effective concentrations of DAGO, DSTBULET, and U50,488 were equally well antagonized by the mu-opioid receptor-selective antagonist naloxone (EC50 of approximately 0.1 microM). Neither the irreversible delta-ligand fentanyl isothiocyanate (1 microM) nor the reversible delta-antagonist ICI 174864 (1 microM) reversed the inhibitory effects of DSTBULET. The inhibitory effects of DAGO and U50,488 were equally well reversed by high concentrations (greater than 0.1 microM) of the kappa-opioid receptor-selective antagonist norbinaltorphimine. The effect of DAGO (1 microM) was already detectable after 1 day in culture, whereas DPDPE (1 microM) had no effect even after 28 days in culture. These data indicate that an homogeneous population of mu-opioid receptors coupled as inhibitors to D1 dopamine receptor-stimulated adenylate cyclase is expressed in rat neostriatal neurons in primary culture. 相似文献
23.
[3H]Spiperone ([3H]SPI) binding sites in rat or bovine striata have been solubilized using CHAPS or digitonin detergents. Solubilized sites retained the binding characteristics of those in native membrane preparations. The same solubilized material, however, did not bind [3H]tyramine ([3H]PTA), thus indicating that [3H]PTA binding sites and DA receptors are different chemico-physical entities. In membrane preparations or crude synaptosomes obtained from the c.striatum of neonatally-rendered hypothyroid rats, when central DA-pathways are impaired, both [3H]PTA binding and [3H]DA uptake processes were markedly decreased, with no effect on [3H]mazindol ([3H]MAZ) binding, compared to euthyroids. Reserpine, a well-known inhibitor of DA-uptake into a variety of secretory vesicles, and a potent in vivo andin vitro inhibitor of [3H]PTA binding, did not affect the [3H]MAZ binding process. This further supported the suggestion that while [3H]PTA binding sites are almost totally associated with the vesicular transporter for DA, [3H]MAZ does label a site involved in the DA-translocation across the neuronal membrane. The latter process seems to be rather insensitive to thyroid hypofunction, when however the intracellular storage of DA might be consistently impaired. In conclusion, PTA might be well exploited as a marker of the DA vesicular transporter through its molecular characterization, whenever possible.Special issue dedicated to Dr. Paola S. Timiras 相似文献
24.
Nefiracetam is a novel pyrrolidone derivative which attenuates scopolamine-induced learning and post-training consolidation
deficits. Given that apomorphine inhibits passive avoidance retention when given during training or in a defined 10–12h post-training
period, we evaluated the ability of nefiracetam to attenuate amnesia induced by dopaminergic agonism. A step-down passive
avoidance paradigm was employed and nefiracetam (3 mg/kg) and apomorphine (0.5 mg/kg) were given alone or in combination during
training and at the 10–12h post-training period of consolidation. Co-administration of nefiracetam and apomorphine during
training or 10h thereafter produced no significant anti-amnesic effect. However, administration of nefiracetam during training
completely reversed the amnesia induced by apomorphine at the 10h post-training time and the converse was also true. These
effects were not mediated by a dopaminergic mechanism as nefiracetam, at millimolar concentrations, failed to displace either
[3H]SCH 23390 or [3H]spiperone binding from D1 or D2 dopamine receptor subtypes, respectively. It is suggested that nefiracetam augments molecular processes in the early stages
of events which ultimately lead to consolidation of memory. 相似文献
25.
This study examined the localized action of neuropeptide Y (NPY) on monoamine transmitter activity in the hypothalamus of
the unrestrained rat as this peptide induced hypothermia, spontaneous feeding or both responses simultaneously. A guide tube
was implanted in the anterior hypothalamic pre-optic area (AH/POA) of Sprague-Dawley rats. Then either control CSF vehicle
or NPY in a dose of either 100 ng/μl or 250 ng/μl was perfused by push-pull cannulae in this structure in the fully sated,
normothermic rat. Successive perfusions were carried out at a rate of 20 μl/min for 6.0 min with an interval of 6.0 min elapsing
between each. Samples of perfusate were assayed by HPLC for their levels of dopamine (DA), norepinephrine (NE), serotonin
(5-HT) and their respective metabolites. Whereas control CSF was without effect on body temperature (Tb) or feeding, repeated perfusions of NPY over 3.0 hr caused dose—dependent eating from 4 to 39 g of food, hypothermia of 0.9
to 2.3°C or both responses concurrently. As the rats consumed 11–39 g of food, the efflux of NE, MHPG, DOPAC and 5-HT was
enhanced significantly, whereas during the fall in Tb the efflux of NE, DOPAC and 5-HIAA from the AH/POA increased. When the Tb of the rat declined simultaneously with eating behavior, the levels in perfusate of DOPAC and HVA increased significantly
while MHPG declined. During perfusion of the AH/POA with NPY the turnover of NE declined while DA and 5-HT turnover increased
during hypothermia alone or when accompanied by feeding. These results demonstrate that the sustained elevation in NPY within
the AH/POA causes a selective alteration in the activity of the neurotransmitters implicated in thermoregulation, satiety
and hunger. These findings suggest that both DA and NE comprise intermediary factors facilitating the action of NPY on neurons
involved in thermoregulatory and ingestive processes. The local activity of NPY on hypothalamic neurons apparently shifts
the functional balance of serotonergic and catecholaminergic neurons now thought to play a primary role in the control of
energy metabolism and caloric intake. 相似文献
26.
Regulation of gap junction coupling in the developing neocortex 总被引:4,自引:0,他引:4
In the developing mammalian, neocortex gap junctions represent a transient, metabolic, and electrical communication system.
These gap junctions may play a crucial role during the formation and refinement of neocortical synaptic circuitries. This
article focuses on two major points. First, the influence of gap junctions on electrotonic cell properties will be considered.
Both the time-course and the amplitude of synaptic potentials depend,inter alia, on the integration capabilities of the postsynaptic neurons. These capabilities are, to a considerable extent, determined
by the electrotonic characteristics of the postsynaptic cell. As a consequence, the efficacy of chemical synaptic inputs may
be crucially affected by the presence of gap junctions.
The second major topic is the regulation of gap junctional communication by neurotransmitters via second messenger pathways.
The monoaminergic neuromodulators dopamine, nordrenaline, and serotonin reduce gap junction coupling via activation of two
different intracellular signaling cascades—the cAMP/protein kinase A pathway and the IP3/Ca2+/protein kinase C pathway, 013 respectively. In addition, gap junctional
communication seems to be modulated by the nitric oxide (NO)/cGMP system. Since NO production can be stimulated by glutamate-induced
calcium influx, the NO/cGMP-dependent modulation of gap junctions might represent a functional link between developing glutamatergic
synaptic transmission and the gap junctional network. Thus, it might be of particular importance in view of a role of gap
junctions during the process of circuit formation. 相似文献
27.
Corticotropin-releasing hormone (CRH) has been shown to be a central mediator for most, if not all, stress-induced responses. Since stressful stimuli may decrease hypothalamic tuberoinfundibular and tuberohypophysial dopaminergic neuronal activities, we aimed to determine whether CRH is involved. Using central administration of various doses of ovine CRH (oCRH; 1, 3 and 10 µg/rat) into the lateral cerebroventricle of either male or female rats, the neurochemical changes in various parts of the central nervous system, including the hypothalamus, were determined by high-performance liquid chromatography at various times after the injection (30, 60, 120 and 240 min). The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG), two major metabolites of dopamine and norepinephrine, respectively, in discrete brain regions were used as indices for catecholaminergic neuron activity. Plasma corticosterone levels increased significantly after all doses of oCRH and at all time points studied. oCRH also exerted significant stimulatory effects on noradrenergic neuron terminals in the frontal cortex, and on dopaminergic neuron terminals in the nucleus accumbens, hypothalamic paraventricular and periventricular nuclei, and intermediate pituitary lobe. Dopaminergic neuron terminals in the median eminence and the neural lobe of the pituitary, however, were not affected. There was no major difference in the responses between male and female rats. We conclude that CRH has a differential effect on central catecholaminergic neurons. 相似文献
28.
Abstract: Effects of ascorbic acid (AA) on 125 I-SCH 23982 binding to D1 dopaminergic receptors in membrane preparations from rat striatum were investigated. AA in the range of 0.03 µ M –0.33 m M inhibited 75% of specific binding of 125 I-SCH 23982 in a dose-dependent manner. At higher concentrations, this inhibition of binding activity by AA was less potent, and 3.3 m M AA inhibited only 30% of specific binding. Reduced glutathione did not alter the inhibition of binding by 0.33 m M AA, but reduced the inhibition by 3.3 m M AA to 8% of specific binding. The loss of specific binding by AA was rescued by 1 m M EDTA, an inhibitor of lipid peroxidation. In the absence of AA, competition experiments with the agonist, dopamine, revealed the presence of high-affinity ( K h = 224.9 ± 48.9 n M ) and low-affinity ( K l = 21,100 ± 2,400 n M ) binding sites. Although the maximum binding of 125 I-SCH 23982 decreased to 40% without affecting the K D value in the presence of 1.67 m M AA, the value of the high-affinity site for dopamine was increased ( K h = 23.3 ± 9.4 n M ) and that of the low-affinity site was decreased ( K l = 136,800 ± 40,900 n M ). These results suggest that AA may affect D1 dopamine receptor function by lipid peroxidation, competition with dopamine for low-affinity sites, and reduced oxidation of dopamine. 相似文献
29.
Abstract: Solubilization of rat striatal membranes with sodium cholate, followed by reconstitution into phospholipid vesicles, leads to a 6.5-fold increase in the agonist high-affinity binding sites of the D1 dopamine receptor. These high-affinity binding sites display differential sensitivity toward temperature. When reconstituted receptors were preincubated for 1 h at 0–4°C (on ice) or at 22°C (room temperature) followed by radioligand binding assays with dopamine, neither the high-affinity values of the receptor for dopamine nor the percent receptors in the high-affinity state (31–39%) were changed from control reconstituted receptors, which were not subject to any preincubations. At 30°C, there was a partial loss in the number of high-affinity D1 receptors with only 25% of the total receptor population in the high-affinity state; there was no change in the affinity values of the high-affinity binding sites. At 37°C, there was a 40% loss in total number of D1 receptor binding sites. All the high-affinity binding sites were lost and the remaining 60% of binding activity represented the low-affinity binding state of the receptor. These results indicate that the high-affinity binding sites of the reconstituted D1 dopamine receptors are uniquely sensitive to higher temperatures. 相似文献
30.
Hideaki Kabuto Isao Yokoi Mineo Takei Tadashi Kurimoto Akitane Mori 《Neurochemical research》1994,19(4):463-467
Serotonin (5-HT) plays an important role in the seizures of El mice since the seizure threshold of El mice correlates with the 5-HT concentration in the central nervous system. In this study, the anticonvulsant effect of a 5-HT reuptake blocker, citalopram, was evaluated behaviorally and biochemically. El mouse convulsions were inhibited by oral administration of citalopram for 2 weeks. Citalopram increased tryptophan and tyrosine amounts, and decreased the 5-HT, 5-hydroxy-indoleacetic acid, kynurenine, and dopamine amounts in the brain. These findings show that citalopram depresses monoaminergic metabolism. Given the known convulsant effect of kynurenine, it is suggested that its decrease by citalopram may involve attenuation of El mice seizures. 相似文献