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1.
In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT1/5-HT2 antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT2 antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT1/5-HT2 but not by selective 5-HT2, antagonists suggests the possibility that 5-HT1 receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.Portions of this research were presented at the Meeting of the Committee on Problems of Drug Dependence Satellite Session (International Study Group Interested in Drugs as Reinforcers and the Society for the Stimulus Properties of Drugs) in Baltimore, MD (1985) 相似文献
2.
Central activation of excitatory amino acid receptors has been implicated in neuropathic pain following nerve injury. In a rat model of painful peripheral mononeuropathy, we compared the effects of non-competitive NMDA receptor antagonists (MK 801 and HA966) and a non-NMDA receptor antagonist (CNQX) on induction and maintenance of thermal hyperalgesia induced by chronic constrictive injury (CCI) of the rat common sciatic nerve. Thermal hyperalgesia to radiant heat was assessed by using a foot-withdrawal test and NMDA/non-NMDA receptor antagonists were administered intrathecally onto the lumbar spinal cord before and after nerve injury. Four daily single treatments with 20 nmol HA966 or CNQX beginning 15 min prior to nerve ligation (pre-injury treatment), reliably reduced thermal hyperalgesia in CCI rats on days 3, 5, 7 and 10 after nerve ligation. Thermal hyperalgesia was also reduced in CCI rats receiving a single post-injury treatment with HA966 (20 or 80 nmol) or MK 801 (5 or 20 nmol) on day 3 after nerve ligation when thermal hyperalgesia was well developed. In contrast, a single post-injury CNQX (20 or 80 nmol) treatment failed to reduce thermal hyperalgesia or to potentiate effects of HA966 or MK 801 (5 or 20 nmol) on thermal hyperalgesia in CCI rats. Moreover, multiple post-injury CNQX treatments utilizing the same dose regime as employed for the pre-injury treatment attenuated thermal hyperalgesia but only when the treatment began 1 or 24 h (but not 72 h) after nerve ligation.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
The mouse model of transcranial permanent occlusion of the middle cerebral artery (tpMCAO) is widely used in stroke research. Here we quantified infarct size using a conventional histological method at several post-ischaemic times, going beyond the commonly analysed period of up to 2 days, following artery occlusion. Two different mouse strains, which are widely used for pharmacological studies of neuroprotection and for genetic engineering, were used. A drill whole was made into the skull of anaesthetised mice and ischaemia was induced by electrocoagulation of the middle cerebral artery. In both mouse strains tested (C57Black/6 and NMRI), the measured infarct volumes decreased significantly during the first days after tpMCAO. Notably, 13 days after surgery, ischaemic and sham-operated animals had indistinguishably small lesions, which where in the range of only 5% of the infarct size on day 2 post-ischaemia. The standard method of calculating oedema and shrinkage correction provided no sufficient explanation for this significant decrease in infarct volume. There was, however, evidence that structural changes in the residual ipsilateral hemisphere may compromise the significance of results arising from the method of calculating oedema and shrinkage correction. In conclusion, our study indicates that the pronounced and fast, time-dependent decrease in histologically defined infarct volume can compromise results when studying the lasting neuroprotective effects of potential drugs. 相似文献
4.
ITP患者骨髓及血液检测指标与疗效关系的探讨 总被引:2,自引:0,他引:2
目的:为观察血小板表面相关抗体G(PaIgG)、外周血血小板计数(BPC)、平均血小板容积(MPV)、骨髓巨核细胞计数(MK)与产板型巨核细胞比例(PPMK)对特发性血小板减少性紫癜(idiopathic thrombocytopenicpurpura,ITP)患者疗效的预计价值。方法:采用Coulter全自动血球分析仪及双抗体夹心ELISA法等,对73例ITP患者治疗前和治疗后的BPC、MPV、 相似文献
5.
中期因子及MVD在胃癌中的表达及临床意义 总被引:2,自引:0,他引:2
目的探讨中期因子(midkine,MK)在胃癌组织中表达及其与微血管密度(MVD)和临床病理特征的关系,探讨影响胃癌患者长期生存的预后因素。方法应用免疫组化两步法检测107例胃癌组织中中期因子和CD34的表达,并以31例正常胃黏膜标本作对照。对CD34阳性血管进行MVD计数,并结合临床资料进行统计学分析。结合随访资料,应用Cox比例风险模型对可能影响胃癌预后结果的参数进行分析。结果胃癌组织中的中期因子阳性表达率分别为69.2%,MVD为32.74±6.46;正常胃黏膜组织中期因子0.00%,MVD为14.55±4.07,胃癌组织中中期因子表达率及MVD均明显高于正常胃黏膜组织(均P〈0.01)。中期因子表达与胃癌的大小、有无淋巴结转移、浸润深度、TNM分期有关(均P〈0.01),而与患者年龄、性别无关。在胃癌组织中中期因子的表达与MVD呈正相关(r=0.592,P〈0.01)。MVD与胃癌的大小、浸润深度、有无淋巴结转移、TNM分期有关(均P〈0.01)。Cox单因素回归分析表明胃癌的大小、浸润深度、有无淋巴结转移、病理分期、中期因子表达与胃癌的预后有关(P〈0.05),而性别、年龄等与预后无关(P〉0.05)。但经Cox多因素回归分析,只有肿瘤的病理分期、MK表达具有独立的预后意义(P〈0.05)。结论在胃癌组织中,中期因子的过度表达可能在肿瘤的血管生成和进展过程中起着重要作用。MK过表达可作为评估胃癌患者预后的独立指标,从而指导胃癌的治疗。 相似文献
6.
The effects of pretreatment with the non-competitive NMDA antagonist (+)MK-801 on the behavioral alterations induced by repeated restraint stress were investigated. Repeatedly stressed (restraint stress 2 h a day × 10 days) mice showed enhanced sensitivity to the inhibitory effects of a low dose of direct dopamine agonist, apomorphine (0.25 mg/kg), on climbing behavior. On the other hand, no changes were observed for the stimulatory effect of the high dose of apomorphine (3 mg/kg) on this behavioral response. Mice pretreated with MK-801 (0.15 mg/kg) before the stressful experience did not show altered response to the low dose of apomorphine (0.25 mg/kg). Finally, ten daily injections with 0.15 mg/kg MK-801 did not affect the behavioral response to the low dose of apomorphine, but enhanced the stimulatory effect of the high dose of the dopaminergic agonist on climbing behavior. Therefore, it is possible that the protective action of MK-801 against stress-induced behavioral alteration is due to changes in sensitivity of postsynaptic receptors. 相似文献
7.
Excitatory amino acids are involved in acute and chronic neurodegenerativediseases.Little is known about the potential consequences of chronic blockade of NMDA receptors (onesubtype of excitatory amino acid receptors).Receptor function measured as 3H-GABA release inculture media after pretreatment with MK801 was studied in rat cortical neurons in primary cultures.Cultured neurons were exposed to 1μmol·L-1 MK801 for 4 days since the 14th day.Glutamate( 1 mmol·L-1 )evoked 3H-GABA release was shown to be significantly increased(control0.2174‰±1.40‰; MK801 treatment 0.763%±0.192%).KCl 40 mmol·L-1 stimulation showedno such effect.This result suggests that the NMDA receptor function of releasing neurotransmitterschanged after chronic treatment with noncompetitive antagonists. 相似文献
8.
目的 观察半胱氨酰白三烯D4(LTD4)及半胱氨酰白三烯受体1拮抗剂MK571对人结肠癌细胞株SW480、Caco-2增殖和凋亡的影响.方法 MTT法检测细胞生长活性;FITC Annexin V/碘化丙啶(PI)双染流式细胞术检测细胞的凋亡率;PI染色细胞,用流式细胞仪检测细胞周期.结果 12.5 ~ 400 μg/L的LTD4对结肠癌SW480细胞有促增殖作用,且存在时效和量效依赖性;而1.6~12.5μg/L的LTD4处理24、48 h,对SW480细胞的增殖抑制作用无明显影响,作用时间延长至72 h,可促进SW480细胞的增殖.50~ 400 μg/L的LTD4对结肠癌Caco-2细胞有促增殖作用,且存在时效和量效依赖性;而1.6-50 μg/L的LTD4对结肠癌Caco-2细胞的影响与对照组相比差异无统计学意义.6.25~200 μmol/L的MK571对结肠癌SW480细胞有抑制作用,且存在时效和量效依赖性;而0.8 ~ 6.25 μmol/L的MK571对SW480细胞的影响与对照组相比无明显差异.25~ 200 μmol/L的MK571对结肠癌Caco-2细胞有抑制作用,且存在时效和量效依赖性;而0.8~ 25 μmol/L的MK571对结肠癌Caco-2细胞的影响与对照组相比差异无统计学意义.与阴性对照组相比,25 ~ 100 μg/L的LTD4对2种结肠癌SW480细胞和Caco-2细胞有促凋亡作用,且存在时效和量效依赖性;而100、200 μmol/L的MK571对2种结肠癌的凋亡无明显作用.与阴性对照组相比,25 ~ 100 μg/L的LTD4可以降低2种结肠癌细胞株G0/G1期比例,增加G2/M及S期比例;而100、200 μmol/L的MK571增加2种结肠癌细胞G0/G1期的比例,降低G2/M及S期比例.结论 LTD4具有促进人结肠癌SW480、Caco-2细胞株增殖的作用,该作用可能的作用机制是抑制凋亡、增加G2/M及S期细胞比例.MK571可抑制2种结肠癌细胞株的增殖,但对凋亡无明显影响,其抑制增殖作用的可能机制是阻滞细胞于G0/G1期. 相似文献
9.
目的探讨宫颈癌患者中期因子表达及与侵袭转移能力的关系.方法选择陕西中医学院第二附属医院妇产科就诊的91例宫颈鳞癌患者,Ⅰ期34例,Ⅱ期33例,Ⅲ期患者24例,对各期患者血清MK、MMP-2、TIMP-2进行检测并对宫颈癌组织行免疫组化染色.结果Ⅱ期患者MK阳性率较Ⅰ期出现显著升高(P<0.05),Ⅲ期患者MK阳性率较Ⅰ期、Ⅱ期组均出现显著升高(P<0.05).免疫组化染色可见随着分期的进展,宫颈癌组织MK免疫组化染色强度逐渐增加.Ⅱ期患者MK及MMP-2较Ⅰ期均出现显著升高(P<0.05),TIMP-2出现下降(P<0.05).Ⅲ期患者MK及MMP-2较Ⅰ期、Ⅱ期组均出现显著升高(P<0.05),TIMP-2出现显著下降(P<0.05).MK与MMP-2呈正相关(P<0.05),与TIMP-2呈负相关(P<0.05).结论随着宫颈癌分期的进展,中期因子表达及与侵袭转移能力增强密切相关,是反映宫颈癌侵袭能力的重要因子. 相似文献
10.