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1.
Heroin self-administration behavior under a progressive ratio (PR) schedule of reinforcement was evaluated in rats. The schedule was designed to restrict drug intake, minimize opiate dependency, and quantify the number of responses emitted (final response ratio) in order to receive a limited number of heroin infusions. Final ratios were found to be stable and did not increase with chronic (31 days) PR reinforcement. The ability of the PR schedule to detect changes in heroin reinforcement was demonstrated by evaluating the effect of naltrexone pretreatment and unit dose alteration on final ratios. Naltrexone (0.4 mg/kg) reduced final ratios and an inverted U dose-response relationship was established for the unit heroin doses 12.5–100 µg/injection. Maximal final ratios occurred with 50 µg/injection heroin reinforcement. This PR schedule may provide a useful method for evaluating the effects of pharmacological manipulations or lesions on opiate reinforcement. 相似文献
2.
The effects of naltrexone (NTX) on the acquisition of ethanol drinking was assessed in rats. NTX (0, 2.5, 5.0, or 10.0 mg/kg) was administered to rats presented with an ascending series of ethanol concentrations (2%, 4%, 6%, and 8% v/v) and water. The 2.5 and 10 mg/kg doses of NTX attenuated the acquisition of voluntary drinking of 8% ethanol, but the 5.0 mg/kg dose of NTX had no effect on ethanol intake. The acquisition paradigm was repeated in experiment 2 with naïve animals that received 0, 5.0, or 7.5 mg/kg of NTX. Neither dose of NTX affected ethanol intake, preference for alcohol, or water intake. Total fluid intake was suppressed in the NTX groups, but only on the second presentations of the 2% and 6% concentrations of ethanol. We suggest that the 2.5 and 10 mg/kg doses of NTX may have attenuated the acquisition of ethanol drinking by at least two different behavioral mechanisms. 相似文献
3.
The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. We have recently shown that ‘illness’-inducing agents, such as intraperitoneally administered lipopolysaccharide (LPS; bacterial endotoxin), can produce prolonged hyperalgesia. This hyperalgesic state is mediated at the level of the spinal cord via activation of the NMDA-nitric oxide cascade. However, prolonged neuronal depolarization is required before such a cascade can occur. The present series of experiments were aimed at identifying spinal neurotransmitters which might be responsible for creating such a depolarized state. These studies show that LPS hyperalgesia is mediated at the level of the spinal cord by substance P, cholecystokinin and excitatory amino acids acting at non-NMDA sites. No apparent role for serotonin or kappa opiate receptors was found. 相似文献
4.
以小鼠心肌组织异位移植和混合淋巴细胞反应为整体和离体模型,观察了阿片受体阻断剂纳曲酮对移植排异反应的影响。结果显示:给动物从术前开始腹腔注射纳曲酮共10天(每日二次,每次5mg/kg)可明显延长移植心肌组织的存活时间;加入纳曲酮(10-4~10-8mol/L)对混合淋巴细胞反应有抑制作用并呈量效关系。同时还观察到,给正常小鼠腹腔注射纳曲酮3天以上,可引起动物脾细胞由ConA诱导的淋巴细胞转化反应受抑制。以上结果说明纳曲酮可抑制移植排异反应,此作用有可能是通过阻断内源性阿片肽所致。 相似文献
5.
The effects of naltrexone on the behavior in mice were investigated by using a multi-dimensional behavioral analyser. Within 15 min following observation, naltrexone preferentially suppressed the linear locomotion at the 10 and 30 mg/kg doses. The results suggest that naltrexone selectively disrupts the linear locomotion without affecting other behaviors in mice. 相似文献
6.
Effective medical treatment for impulsive aggression and several impulse control disorders is needed. Disinhibited, impulsive behavior of e.g. murderers, arsonists, suicidal patients, and patients suffering from antisocial personality or substance abuse disorders has been associated with signs of a deficiency in brain serotonin (5-HT) systems. Depletion of brain 5-HT consistently produces disinhibition and aggression also in experimental animals. The present series of experiments using a modified Vogel’s conflict test indicates that the disinhibitory behavior of 5-HT-lesioned rats can be reversed by the commonly used opiate receptor antagonist naloxone at doses (0.1–5.0 mg/kg, s.c.) that do not significantly affect behavior in sham-lesioned controls. Moreover, this effect of naloxone, which resembles that previously observed after administration of negative modulators of γ-aminobutyric acidA (GABAA)/benzodiazepine receptor complexes, was reversed by a low inert dose (2.0 mg/kg, i.p.) of amobarbital. Furthermore, both naloxone (5.0 mg/kg, s.c.) and Ro 15-4513 (1.0 mg/kg, p.o.; a partial inverse agonist at benzodiazepine receptors) significantly decreased the number of attacks and the time spent in aggressive acts in 5,7-DHT-lesioned male residents. These results taken together with previous behavioral and neurochemical data suggest that the behavioral effects of naloxone observed here may involve an antagonistic action at brain γ-aminobutyric acidA (GABAA)/benzodiazepine receptor complexes. Thus, naloxone, its stable analogue naltrexone or other weak negative modulators of brain GABAA/benzodiazepine receptor complexes may represent a new pharmacological principle for the treatment of impulse control disorders. 相似文献
7.
Nestby P Schoffelmeer AN Homberg JR Wardeh G De Vries TJ Mulder AH Vanderschuren LJ 《Psychopharmacology》1999,142(3):309-317
It has been postulated that opioid systems in the brain may play a role in ethanol reinforcement. In this respect, μ- and
δ-opioid receptors may mediate the rewarding effects whereas κ receptors are thought to mediate the aversive effects of opioids.
Accordingly, long-acting benzomorphans such as bremazocine, that simultaneously act as μ and δ receptor antagonists and κ receptor agonists may be particularly effective in reducing ethanol self-administration. Therefore, we studied the effect
of bremazocine on oral ethanol self-administration in rats using a paradigm [unrestricted free-choice drinking of 10% (v/v)
ethanol], previously shown to cause long-term neuroadaptations in the nucleus accumbens and caudate putamen. Bremazocine (0.1 mg/kg,
once daily for five consecutive days) reduced ethanol drinking by about 50% during the active period of the animals, whereas
the intake of sucrose (3–10% w/v) was affected neither in naive nor in ethanol-experienced rats. This effect of bremazocine
appeared not to be secondary to its acute sedative effect or the slight increase in total fluid consumption. Unlike bremazocine,
the selective κ-opioid receptor agonist U50,488H (10 mg/kg, once daily) inhibited ethanol drinking only during the first of 5 treatment days
and the opioid receptor antagonist naltrexone (0.3–10 mg/kg, once daily) only caused a modest (about 20%) suppression of ethanol
drinking during the first hours after drug injection. Thus, bremazocine appears to be far more potent than the clinically
applied drug naltrexone in this respect. Our data further support the role of opioid receptors in ethanol reinforcement and
indicate that long-acting mixed-action opioids such as bremazocine may be useful as adjuvants for the clinical management
of ethanol addiction.
Received: 1 July 1998/Final version: 3 September 1998 相似文献
8.
J. Staedt F. Wassmuth G. Stoppe G. Hajak A. Rodenbeck W. Poser E. Rüther 《European archives of psychiatry and clinical neuroscience》1996,246(6):305-309
Previous studies have described sleep disturbance secondary to chronic opiate use and abuse. Drug-dependency insomnia is of interest because chronic sleep disturbances can promote depressive symptoms which could lead to a drug relapse. For the first time we compared the polysomnographic parameters of 10 methadone-substituted outpatients and 10 naltrexone-treated outpatients. Methadone (-opioid agonist) produced a marked fragmentation of the sleep architecture with frequent awakenings and a decrease in EEG arousals. In comparison with methadone and controls, the naltrexone (-opioid antagonist) group showed the shortest sleep latency and the longest total sleep time. These data indicate that -agonists and -antagonists have different effects on sleep. The implications, especially the involvement of opioid-dopamine interactions on sleep and movements during sleep, are discussed. 相似文献
9.
Summary Abstinence signs were precipitated in rats by naloxone (1 mg·kg-1 s.c.) injected at various times (from 1.5 to 16 h) after a single dose of morphine hydrochloride (15 or 50 mg·kg-1 s.c.) administered incaqueous solution. Increasing the dose of morphine increased the latency of the phenomena and the duration of the underlying state shifts of signs as described by Bläsig et al. (1974) in chronically morphinized rats also occurred when increasing the dose of morphine and the time interval between the injections of morphine and of naloxone. Naltrexone and diprenorphine were also effective. These three antagonists, given before morphine, were able to prevent precipitated abstinence: however, naloxone was almost ineffective when the higher dose of morphine was used and when the time interval was long. In these latter conditions, naltrexone was definitely more effective and longer acting and diprenorphine still more so. The same characteristics were found for the protective action of the three antagonists in acutely morphinized mice and the same order for their potencies in precipitating abstinence in acutely morphinized mice. Like naloxone, naltrexone and diprenorphine facilitated a nociceptive reaction in normal mice.The abstinence signs precipitated in acutely morphinized rats or mice are probably not unmasked excitatory effects of morphine as such effects should have been increased rather than inhibited by previous administration of specific antagonists; they might correspond to potentiated effects of the antagonists themselves. The prevention by specific antagonists of the abstinence syndrome is most simply interpreted by antagonism (direct or indirect) of dependence induction, but other interpretations are not excluded. 相似文献
10.
综合疗法对海洛因依赖患者复吸的影响 总被引:4,自引:6,他引:4
目的:观察海洛因依赖患者在住院过程中进行综合性治疗(美沙酮递减脱瘾、生物体适应性平衡调整、心理干预、纳曲酮的应用)对出院后复吸的影口向。方法:将海洛因依赖患者90例,按随机化方法分为综合治疗组、美沙酮纳曲酮组及单纯美沙酮治疗组各30例。观察三种治疗方案临床疗效及出院后半年复吸率。结果:综合治疗方案及美沙酮纳曲酮治疗方案在控制脱毒后稽延性戒断症状,缓解焦虑情绪、改善睡眠及降低心理渴求方面均优于单纯美沙酮脱瘾治疗(P<0.01),且出院后半年操守人数亦有显著差异(P<0.01)。综合治疗组半年复吸率降低66.67%。综合治疗方案的临床疗效及防复吸效果又优于美沙酮纳曲酮组(P<0.05)。结论:综合治疗方案临床操作简单易行,临床疗效显著,对海洛因依赖患者脱毒出院后的复吸起到积极预防作用,值得推广。 相似文献