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1.
目的:建立苯环利定(Phencyclidine,PCP)诱导精神分裂症小鼠模型,考察活化的蛋白激酶C受体1(Receptor for activated C kinase 1,RACK1)在脑内的表达变化。方法:将48只雄性C57BL/6小鼠随机分为对照组和精神分裂症模型组(n=24)。模型组小鼠皮下注射PCP1.5 mg?kg-1,对照组皮下注射等体积生理盐水,连续注射7d后进行刻板行为实验,记录刻板行为评分,并采用免疫荧光染色测定全脑RACK1的表达情况。结果:与对照组相比,PCP皮下注射导致小鼠反复摇头、转圈等刻板行为明显增加(P<0.05),且小鼠脑内小胶质细胞明显增生活化。免疫荧光检测结果显示,PCP小鼠海马RACK1表达明显增强,主要表达于神经元,未见与小胶质细胞的共定位。结论:精神分裂症小鼠的刻板行为可能与海马神经元RACK1高表达相关。  相似文献   
2.
《Vaccine》2015,33(48):6545-6551
Immunotherapy has a great potential of becoming a new therapeutic strategy in the treatment of addiction to psychoactive drugs. It may be used to treat addiction but also to prevent neurotoxic complications of drug overdose. In preclinical studies two immunological methods have been tested; active immunization, which relies on the administration of vaccines and passive immunization, which relies on the administration of monoclonal antibodies. Until now researchers have succeeded in developing vaccines and/or antibodies against addiction to heroin, cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has been confirmed in preclinical studies. At present, clinical studies are being conducted for vaccines against nicotine and cocaine and also anti-methamphetamine monoclonal antibody. These preclinical and clinical studies suggest that immunotherapy may be useful in the treatment of addiction and drug overdose. However, there are a few problems to be solved. One of them is controlling the level of antibodies due to variability between subjects. But even obtaining a suitable antibody titer does not guarantee the effectiveness of the vaccine. Additionally, there is a risk of intentional or unintentional overdose. As vaccines prevent passing of drugs through the blood/brain barrier and thereby prevent their positive reinforcement, some addicted patients may erroneously seek higher doses of psychoactive substances to get “high”. Consequently, vaccination should be targeted at persons who have a strong motivation to free themselves from drug dependency. It seems that immunotherapy may be an opportunity for effective treatment of drug addiction if directed to adequate candidates for treatment. For other addicts, immunotherapy may be a very important element supporting psycho- and pharmacotherapy.  相似文献   
3.
Context. Emergency medical workers often experience violence while performing their job functions. Phencyclidine (PCP)-intoxicated patients are often violent and difficult to control physically. A chemical restraint is frequently needed to assist in protecting both patients and staff from agitated persons. Objective. This study evaluated haloperidol as a chemical restraint in PCP-intoxicated patients. Methods. This is a retrospective case series of all PCP-positive patients who received haloperidol for behavioral control from April 2008 to April 2011 at a single large (944 bed), urban, tertiary-care hospital. All patients receiving haloperidol and having a toxicology screen positive for PCP were identified using an electronic medical record. Identified cases were then manually reviewed by investigators for adverse events. Results. Subjects included 59 adult patients who were acutely agitated requiring chemical restraint or sedation with haloperidol, and who tested positive for PCP. There were 20 females and 39 males, ranging in age from 19 to 54 years. Patients received haloperidol via the PO, IM, or IV routes in doses ranging from 1 to 10 mg. There were two adverse events (mild hypoxia and mild hypotension) found during chart review; neither were serious nor required change in patient disposition. Conclusions. In this study, haloperidol does not seem to cause harm when used in the management of PCP-intoxicated patients. Caution must always be exercised in the use of chemical restraint; further prospective study is warranted.  相似文献   
4.
Ketamine's history begins in the fifties in Detroit, at Parke-Davis laboratories. In 1956, Maddox synthetized phencyclidine or PCP. Domino studied PCP effects in animals and in 1958, Greifenstein made the first trials of PCP in humans under the name of Sernyl. Sernyl elicited severe excitation with a prolonged postoperative recovery. Because of its psychedelic effects, it became a street-drug under the name of “angel dust”. Calvin Stevens synthesized ketamine in 1962. The drug was studied in humans in 1964, by Domino and Corssen who described the so-called “dissociative anesthesia”. Ketamine was patented in 1966 under the name of Ketalar for human use and was administered to soldiers during the Vietnam war. The psychedelic effects and the arrival of propofol prompted the shelving of ketamine. However, the discovery of the NMDA-receptor and its non-competitive inhibition by ketamine revolutionized the pathophysiology of hyperalgesia and mental functioning. In early 1990s, the discovery of opioid-induced hyperalgesia elicited a paradigm shift in the management of pain, and a comeback of ketamine, as an anti-hyperalgesic drug. Ketamine is nowadays under the spotlight in the field of treatment-resistant depression and has been proposed as a potential fast antidepressant in patients with high suicidal risk.  相似文献   
5.
Introduction. Methoxphenidine is a novel dissociative designer drug of the diarylethylamine class which shares structural features with phencyclidine (PCP), and is not at present subject to restrictive regulations. There is very limited information about the acute toxicity profile of methoxphenidine and the only sources are anonymous internet sites and a 1989 patent of the Searle Company. We report a case of analytically confirmed oral methoxphenidine toxicity. Case details. A 53-year-old man was found on the street in a somnolent and confusional state. Observed signs and symptoms such as tachycardia (112 bpm), hypertension (220/125 mmHg), echolalia, confusion, agitation, opisthotonus, nystagmus and amnesia were consistent with phencyclidine-induced adverse effects. Temperature (99.1°F (37.3°C)) and peripheral oxygen saturation while breathing room air (99%) were normal. Laboratory analysis revealed an increase of creatine kinase (max 865 U/L), alanine aminotransferase (72 U/L) and gamma-glutamyl transpeptidase (123 U/L). Methoxphenidine was identified by a liquid chromatography tandem mass spectrometry toxicological screening method using turbulent flow online extraction in plasma and urine samples collected on admission. The clinical course was favourable and signs and symptoms resolved with symptomatic treatment. Conclusion. Based on this case report and users’ web reports, and compatible with the chemical structure, methoxphenidine produces effects similar to those of the arylcyclohexylamines, as PCP.  相似文献   
6.

Introduction

Over the past decade, there has been a sharp increase in the number of newly identified synthetic drugs. These new drugs are often derivatives of previously abused substances but have unpredictable toxicity. One of these drugs is gacyclidine, a derivative of phencyclidine (PCP). Gacyclidine has been studied as a neuroprotective agent in trauma and as a therapy of soman toxicity. There are no previous reports of its use as a drug of abuse.

Case Reports

During a two-month period in the summer of 2013, a series of patients with severe agitation and end-organ injury were identified in an urban academic Emergency Department (ED). A urine drug of abuse screen was performed on all patients, and serum samples were sent for comprehensive toxicology analysis. A total of five patients were identified as having agitation, rhabdomyolysis, and elevated troponin (Table 1). Three of the five patients reported use of methamphetamine, and all five patients had urine drug screens positive for amphetamine. Comprehensive serum analysis identified methamphetamine in three cases, cocaine metabolites in one case, and a potential untargeted match for gacyclidine in all five cases. No other drugs of abuse were identified.

Discussion

This is the first series of cases describing possible gacyclidine intoxication. The possible source of the gacyclidine is unknown but it may have been an adulterant in methamphetamine as all patients who were questioned reported methamphetamine use. These cases highlight the importance of screening for new drugs of abuse when patients present with atypical or severe symptoms. Gacyclidine has the potential to become a drug of abuse both by itself and in conjunction with other agents and toxicity from gacyclidine can be severe. It is the role of the medical toxicology field to identify new agents such as gacyclidine early and to attempt to educate the community on the dangers of these new drugs of abuse.  相似文献   
7.
Repeated administration of phencyclidine (PCP), an N-methyl-d-aspartate (NMDA) receptor antagonist, during development, may result in neuronal damage that leads to behavioral deficits in adulthood. The present study examined the potential neurotoxic effects of PCP exposure (10 mg/kg) in rats on postnatal days (PNDs) 7, 9 and 11 and the possible underlying mechanism(s) for neurotoxicity. Brain tissue was harvested for RNA extraction and morphological assessments. RNA was collected from the frontal cortex for DNA microarray analysis and quantitative RT-PCR. Gene expression profiling was determined using Illumina Rat Ref-12 Expression BeadChips containing 22,226 probes. Based on criteria of a fold-change greater than 1.4 and a P-value less than 0.05, 19 genes including NMDAR1 (N-methyl-d-aspartate receptor) and four pro-apoptotic genes were up-regulated, and 25 genes including four anti-apoptotic genes were down-regulated, in the PCP-treated group. In addition, the schizophrenia-relevant genes, Bdnf (Brain-derived neurotrophic factor) and Bhlhb2 (basic helix-loop-helix domain containing, class B, 2), were significantly different between the PCP and the control groups. Quantitative RT-PCR confirmed the microarray results. Elevated neuronal cell death was further confirmed using Fluoro-Jade C staining. These findings support the hypothesis that neurodegeneration caused by PCP occurs, at least in part, through the up-regulation of NMDA receptors, which makes neurons possessing these receptors more vulnerable to endogenous glutamate. The changes in schizophrenia-relevant genes after repeated PCP exposure during development may provide important information concerning the validation of an animal model for this disorder.  相似文献   
8.
Bi-acetylated l-stepholidine (l-SPD-A), a novel derivate of l-stepholidine (l-SPD), possesses a pharmacological profile of D1/5-HT1A agonism and D2 antagonism. In the present study, we examined the potential antipsychotic effect of l-SPD-A in a phencyclidine (PCP)-induced rat model of schizophrenia. Pretreatment with l-SPD-A blocked acute PCP-induced hyperlocomotion and reversed prepulse inhibition (PPI) deficits. Chronic l-SPD-A administration (i.p., 10 mg/kg/day for 14 days) improved social interaction and novel object recognition impairments in rats that were pretreated with PCP (i.p., 5 mg/kg/day for 14 days). Moreover, in a conditioned avoidance response (CAR) test, l-SPD-A, with either i.p. or oral administration, significantly decreased active avoidance without affecting the escape response of rats. Importantly, compared to that of the parent compound l-SPD, l-SPD-A showed stronger suppression of CARs. Lastly, using a [35S]GTPγS binding assay, we demonstrated that l-SPD-A improved impaired dopamine D1 receptor function in the prefrontal cortex (PFC) in chronic PCP-treated rats. Taken together, these results indicate that l-SPD-A was not only effective against the hyperactivity, but also improved the sensorimotor gating deficit, social withdrawal and cognitive impairment in an animal model of schizophrenia. The present data suggest that l-SPD-A, a potential neurotransmitter stabilizer, is a promising novel candidate drug for the treatment of schizophrenia.  相似文献   
9.
目的研究精神分裂症动物模型大鼠前脑内侧束毁损后神经递质的变化。方法用苯环己哌啶(Phencyclidine,PCP)建立精神分裂症的动物模型。将动物分成模型组和毁损组。采用高效液相色谱分析的方法在体检测两组大鼠额叶皮层、杏仁核及海马中神经递质DA和5-HT的含量。结果显示模型组和毁损组大鼠DA和5-HT的含量有显著性差异。结论精神分裂症的动物模型与神经递质DA和5-HT密切相关,通过毁损前脑内侧束可以调节神经递质DA和5-HT的释放,缓解精神分裂症的症状。  相似文献   
10.
In the staircase test, a naive mouse is placed in a Plexiglas chamber containing a five-step staircase, and the number of rearings and steps climbed are recorded for 3 min. A claim for drug-class specificity has been made because conventional anxiolytics reduced rearings at doses that did not reduce steps climbed, while non-anxiolytics affected both measures in parallel. In the present study chlordiazepoxide, meprobamate, and ethanol registered the expected true positive effect by reducing rearings at doses that did not reduce steps climbed. Nicotine, which has some clinical anxiolytic action, registered a small true positive. The benzodiazepine anxiolytic alprazolam reduced both measures, a false negative, although it reduced rearings more than steps climbed. The putative novel anxiolytics CGS 9896, ketanserine, and tracazolate registered negatives, as did the known clinical anxiolytic buspirone. The non-anxiolytics phencyclidine and phenacetin registered true negatives, but morphine registered a clear false positive. The anxiogenics FG 7142 and pentylenetetrazol produced no significant effects. Because of the equivocal false negative for alprazolam, the clear false negative for buspir-one, and the clear false positive for morphine, we concluded that the test lacks the degree of therapeutic-class specificity previously proposed but may still be useful in basic research.  相似文献   
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