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51.
Ugarte YV Rau KS Riddle EL Hanson GR Fleckenstein AE 《European journal of pharmacology》2003,472(3):165-171
Multiple high-dose administrations of the dopamine-releasing agent, methamphetamine, rapidly and persistently decrease vesicular dopamine uptake in purified vesicles prepared from striata of treated rats. Because important differences in the neurotoxic effects of stimulants have been documented in rats and mice, the purpose of this study was to determine if methamphetamine-induced effects in rats occur in mice and to elucidate mechanisms underlying these effects. Results reveal methamphetamine treatment rapidly decreased mouse striatal vesicular dopamine uptake; a phenomenon associated with a subcellular redistribution of vesicular monoamine transporter-2 (VMAT-2) immunoreactivity. Both methamphetamine-induced hyperthermia and dopamine D2 receptor activation contributed to the stimulant-induced deficits in vesicular dopamine uptake. Unlike methamphetamine, the dopamine reuptake inhibitors, methylphenidate and cocaine, rapidly increased vesicular dopamine uptake. The implications of these phenomena are discussed. 相似文献
52.
Neurochemical and behavioral differences between d-methamphetamine and d-amphetamine in rats 总被引:3,自引:2,他引:1
Abstract
Rationale. Methamphetamine (METH) and amphetamine (AMPH) are both abused psychostimulants. Although METH is generally accepted to be
more addictive and potent than its analogue AMPH, there are no known neurobiological differences in action between the two
drugs that may account for such differences.
Objective. METH and AMPH were compared to determine potential mechanisms for such differences between the two drugs in order to provide
new targets for the treatment of METH addiction.
Methods. Using in vivo microdialysis on rats, dopamine (DA), DA metabolites, and glutamate (GLU) release in the nucleus accumbens
(NAC) and prefrontal cortex (PFC) were measured after administration of 2 mg/kg, IP, of METH or AMPH. Based on the neurochemical
differences between METH and AMPH, a locomotor activity study was designed to assess differences in locomotor activation for
a range of doses (1–4 mg/kg, IP) of METH and AMPH and after pretreatment with intra-accumbens GLU antagonists.
Results. METH and AMPH raised NAC DA levels to a similar degree. In the PFC, both METH and AMPH raised DA levels, but METH was less
effective than AMPH. In the NAC, AMPH raised GLU levels but METH did not. In the PFC, METH raised GLU levels but AMPH did
not. The locomotor activity dose response curve for METH had a lower peak than that of AMPH. This difference was blocked by
pretreatment with either the GLU NMDA antagonist AP5 or the GLU AMPA antagonist DNQX locally in the NAC.
Conclusions. This study reveals several previously unknown neurochemical and behavioral differences between METH and AMPH. Based on these
results, it is suggested that new pharmacotherapeutic agents that produce augmentations of NAC GLU or PFC DA activity, or
perhaps inhibition of PFC GLU activity, may someday be useful for the treatment of METH addiction.
Electronic Publication 相似文献
53.
Morita T Sonoda R Nakato K Koshiya K Wanibuchi F Yamaguchi T 《Psychopharmacology》2000,148(3):281-288
Rationale: Phencyclidine (PCP) and methamphetamine (MAP) are known as psychotomimetic agents. Both agents produce behavioral alterations
in animals. Objective: The present study investigated the difference in behavioral alterations in rats induced by these two psychotomimetic agents
using the hole board apparatus (HBA). In addition, mechanisms underlying PCP-induced behavioral changes were also investigated.
Methods: After the administration of PCP (1–4 mg/kg SC) or MAP (1–4 mg/kg SC), locomotor activity and dipping behavior were assessed
using HBA. Effect of selective NMDA antagonists, (+)MK801 and 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP),
on rat behaviors were also assessed. The effects of d-alanine (d-Ala), a coagonist of NMDA receptors, or neuroleptics, haloperidol, clozapine and risperidone, on PCP-induced behavioral changes
were investigated. Results: PCP increased locomotor activity and decreased exploratory behaviors of rats in HBA. On the other hand, MAP increased locomotor
activity but did not decrease exploratory behaviors. (+)MK-801 produced hyperactivity as well as decreased exploratory behaviors,
eliciting behavioral changes very similar to those of PCP. CPP decreased the exploratory behavior but failed to produce hyperactivity.
d-Ala attenuated both behavioral changes induced by PCP. Three neuroleptics tested here inhibited hyperactivity but did not
attenuate decreases in exploratory behavior. Conclusion: These results suggest that PCP-induced decrease in exploratory behavior are attributable to antagonism of NMDA receptors
and may not involve dopaminergic transmission via D2 receptors.
Received: 24 May 1999 / Final version: 16 August 1999 相似文献
54.
55.
Rationale: The phenomenon of sensitization has been theoretically implicated in mediating various aspects of drug addiction. Recent
dose-response studies demonstrated that pretreatment with the putative anti-addictive agent, ibogaine (IBO), and a synthetic
iboga alkaloid congener, 18-methoxycoronaridine (18-MC), increase the potency of cocaine to elicit behavioral sensitization,
an effect proposed to contribute, in part, to their ability to attenuate drug self-administration. Objectives: As abuse of the methylated amphetamine derivative, methamphetamine (METH), is a growing public health concern, the present
study determined the interactions between IBO and 18-MC and the expression of METH-induced behavioral sensitization. Methods: The effects of pretreatment with 18-MC (40 mg/kg, IP, 19 h earlier) on the expression of METH-induced locomotion (0, 0.25,
0.5, 1 and 2 mg/kg, IP) and the effects of pretreatment with either IBO or 18-MC on the expression of METH-induced stereotypy
(2 and 4 mg/kg, IP) were assessed in rats treated chronically with either METH (4 mg/kg daily for 7 days) or saline. Results: Compared to vehicle-pretreated controls, 18-MC produced an overall enhancement in METH-induced locomotion in rats treated
chronically, but not acutely, with METH. In addition, both iboga agents increased the stereotypic response to METH. Conclusions: Iboga agents augment both the locomotor and stereotypic effects of METH in a manner consistent with previous reports for
cocaine. Thus, it appears that iboga agents interact in a similar manner with the neural mechanisms mediating motor hyperactivity
induced by the chronic administration of stimulant drugs.
Received: 17 December 1999 / Accepted: 26 April 2000 相似文献
56.
Hiroshi Ujike Kazufumi Akiyama Hiroshi Nishikawa Taichi Onoue Saburo Otsuki 《Brain research》1991,540(1-2):159-163
To examine the possible involvement of D1 dopamine receptors in behavioral sensitization induced by subchronic methamphetamine (MAP) administration, regional D1 receptors labeled with [3H]SCH 23390 were examined using binding assay and quantitative autoradiography. Rats received 4 mg/kg/day MAP (i.p.) for 14 days, and were decapitated after an abstinence period of 24 h, 7 days or 21 days. In MAP-treated rats, a significant decrease in Kd in the mesolimbic area was observed 24 h but not 7 days after the last injection. Neither Kd nor Bmax changed in the striatum or medial prefrontal cortex of MAP-treated rats after any period of abstinence. Autoradiography revealed a significant increase in specific [3H]SCH 22390 binding in the lateral part of the substantia nigra pars reticulata (SNr) of MAP-treated rats. Since this increase lasted up to 21 days after cessation of subchronic MAP administration, it is suggested that lasting increase in the nigral D1 receptors may be associated with the biological changes underlying MAP-induced behavioral sensitization. 相似文献
57.
Summary Qualitative and quantitative analysis of methamphetamine and amphetamine in biologic materials was carried out by gas chromatography/mass spectrometry. A deuterium-labeled methamphetamine was employed as an internal standard with a detection limit of 50 pg and absolute stability and reproducibility. Blood was found to be the best material for estimation of the toxicity of the stimulant drug. It can be replaced by muscle which contains methamphetamine concentrations close to those of blood. The authors' classification of the toxic blood levels of methamphetamine from therapeutic to fatal doses was confirmed by additional data obtained from new case studies.Supported by a grant-in-aid for scientific research in 1983/1984 from the Japanese Ministry of Education 相似文献
58.
Effects of MDMA, methamphetamine and methylphenidate on repeated acquisition and performance in rats
M. Galizio P. McKinney D.T. Cerutti R.C. Pitts 《Pharmacology, biochemistry, and behavior》2009,94(2):305-311
Repeated-acquisition procedures that include performance controls for effects not specific to acquisition permit the assessment of drug effects on learning on a within-subject, within-session basis. Despite the advantages of this methodology, few studies have examined effects of psychomotor stimulants on repeated acquisition in rodents. The purpose of the present study was to investigate the effects of methylenedioxymethamphetamine (MDMA, 0.3–10 mg/kg), methamphetamine (MA, 0.1–3 mg/kg) and methylphenidate (MPD,1–17 mg/kg) using repeated-acquisition procedures with performance controls in rats using a touch-screen apparatus. Rats were presented a 2 × 3 array of stimuli using a computer touch-screen and nose-pokes to target locations within the array were reinforced. In the acquisition component, the correct location changed across sessions, whereas during the performance component, the correct location was constant across sessions. All three drugs reduced accuracy of responding to target locations in a dose-dependent fashion. None of the compounds enhanced learning at any dose. MPD and MA produced significant disruptions of acquisition accuracy only at doses that also disrupted performance, but the 3 mg/kg dose of MDMA impaired acquisition of target responding without affecting performance. The selective impairment of acquisition found in the present study adds to the evidence of learning and memory disruption produced by acute MDMA administration and raise questions about the mechanisms for these actions. 相似文献
59.
Prospective memory impairment in former users of methamphetamine 总被引:1,自引:1,他引:0
Rationale Considerable research indicates that methamphetamine use is associated with neurocognitive impairment, but no empirical study
to date has assessed whether these difficulties extend to memory for future intentions (prospective memory).
Objectives The present study assessed prospective performance on a laboratory measure of prospective memory that closely represents the
types of prospective memory tasks that actually occur in everyday life and provides an opportunity to investigate the different
sorts of prospective memory failures that occur (“Virtual Week”).
Materials and methods Twenty adults with confirmed history of methamphetamine use and dependence, currently engaged in rehabilitation and confirmed
to be abstinent for an average period of 6 months, and 20 methamphetamine-naive participants were tested on Virtual Week.
Various other aspects of cognitive function were also assessed, including retrospective memory and executive functioning.
Results Methamphetamine users were significantly impaired on Virtual Week, and these deficits did not vary as a function of specific
prospective memory task demands. Of all the cognitive measures, cognitive inhibition shared greatest variance with group effects
on the prospective memory measure.
Conclusions Prospective memory performance is sensitive to prior methamphetamine use even well into abstinence. Methamphetamine users
experience generalized difficulties with prospective memory, suggesting that these deficits are likely to have important implications
for day-to-day functioning. 相似文献
60.
B. A. Johnson John D. Roache Patrick S. Bordnick Nassima Ait-Daoud 《Psychopharmacology》1999,144(3):295-300
Rationale: Dopamine (DA) pathways in the midbrain mediate d-methamphetamine’s rewarding effects associated with its abuse liability. Isradipine, a dihydropyridine-class calcium channel
antagonist, reduces the rewarding effects of psychostimulants such as cocaine and d-amphetamine, presumably by antagonizing these central DA pathways. This is the first experiment to test the hypothesis that
the rewarding effects of d-methamphetamine, like other psychostimulants, can be reduced by isradipine. Objective: We studied the effects of high dose isradipine (0.21 mg/kg orally), on the positive subjective effects associated with the
abuse liability of low and high dose d-methamphetamine (0.21 mg/kg and 0.42 mg/kg orally, respectively). Methods: Using a double-blind, double-dummy, placebo-controlled, Latin-Square, cross-over design, 18 healthy male and female volunteers
received each of the following six treatments separated by a rest period of 2–7 days: a) placebo+placebo; b) low-dose d-methamphetamine+placebo); c) high-dose d-methamphetamine+placebo; d) high dose isradipine+placebo); e) low-dose d-methamphetamine+high dose isradipine, and f) high-dose d-methamphetamine+high dose isradipine. Results: d-Methamphetamine produced orderly increases in positive subjective measures of both stimulation and mood. Pre-treatment with
isradipine significantly reduced some of these positive subjective effects and craving for d-methamphetamine. Conclusion: Isradipine as an anti-reward or craving reducing medication is a promising therapeutic agent for the treatment of d-methamphetamine dependence.
Received: 17 November 1998 / Final version: 4 February 1999 相似文献