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101.
目的 采用网络药理学与分子对接法探索疏风解毒胶囊治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制与活性成分。方法 借助TCMSP数据库检索疏风解毒胶囊组成药材板蓝根、虎杖、连翘、芦根、败酱草、马鞭草、柴胡、甘草的化学成分和作用靶点,通过Swiss Target Prediction数据库剔除可能性为0的靶点。以“冠状病毒(coronavirus)”“肺炎(pneumonia)”“咳嗽(cough)”“发热(fever)”为检索词在GeneCards及OMIM数据库中检索疾病相应靶点。通过Uniprot数据库校正靶点名称,取疏风解毒胶囊与疾病靶点交集,进而运用Cytoscape 3.7.2软件构建中药-化合物-靶点网络进行可视化,通过DAVID数据库进行GO功能富集分析和KEGG通路富集分析,预测交集靶点作用机制,并绘制柱状图及气泡图进行可视化。然后将所有化合物与新型冠状病毒(SARS-CoV-2)3CL水解酶进行对接,选取结合能最小的前5个化合物与血管紧张素转化酶II(ACE2)进行对接。结果 中药-化合物-靶点网络包含了8种中药,157个化合物和相应靶点260个,关键靶点涉及PTGS2、ESR1、AR等。GO功能富集分析得到条目393个(P<0.05),KEGG通路富集分析筛选得到139条信号通路。分子对接结果显示6-(3-氧吲哚-2-亚立德)吲哚[2,1-b]喹唑啉-12-酮、荷包牡丹碱、大黄素甲醚葡萄糖苷、双氢轮叶十齿草碱和甘草异黄烷酮5个核心化合物与SARS-CoV-2 3CL水解酶及ACE2的结合能较推荐化学药小。结论 疏风解毒胶囊中的化合物能通过与SARS-CoV-2 3CL水解酶及ACE2结合作用于PTGS2、ESR1、AR等靶点调节人巨细胞病毒感染、卡波西肉瘤相关疱疹病毒感染、IL-17信号通路等信号通路、小细胞肺癌等发挥治疗COVID-19作用。 相似文献
102.
一叶秋碱和荷包牡丹碱催醒作用的实验研究 总被引:4,自引:2,他引:4
目的分析静脉麻醉药硫喷妥钠、羟丁酸钠、依托咪酯、异丙酚和氯胺酮全麻效应与GABAA受体的关系.方法给小鼠分别腹腔注射麻醉剂量的上述药物,待小鼠翻正反射消失后1min,静脉注射一叶秋碱5mg/kg(0.1ml/10g)或侧脑室注射荷包牡丹碱0.3μg(10μl),对照组分别注射同等剂量的生理盐水或人工脑脊液,观察并记录各组的翻正反射消失持续时间.结果一叶秋碱使依托咪酯的翻正反射消失持续时间由(12.8±7.1)min缩短为(6.5±2.8)min(P<0.05),却不能缩短硫喷妥钠、羟丁酸钠、异丙酚和氯胺酮麻醉小鼠的翻正反射消失持续时间;而荷包牡丹碱对于上述5种静脉麻醉药均不能缩短其翻正反射消失持续时间.结论一叶秋碱对依托咪酯的全麻效应有一定的非特异性拮抗作用,但不能拮抗硫喷妥钠、羟丁酸钠和异丙酚的全麻效应;荷包牡丹碱对于这5种静脉麻醉药的全麻效应均无拮抗作用.结果提示GABAA受体GABA位点并非硫喷妥钠、羟丁酸钠、托咪酯、异丙酚和氯胺酮全麻作用的主要靶位. 相似文献
103.
The relationship between neurite extension and phospholipid metabolism in PC12 cells 总被引:13,自引:0,他引:13
A E Traynor 《Brain research》1984,316(2):205-210
NGF stimulates a variety of changes in PC12 cells. These include neurite extension and an increase in the metabolism of phosphatidylinositol and phosphatidic acid (the so-called 'PI effect'). Cyclic AMP has been postulated to mediate many of the effects of NGF on PC12 cells, and we recently found that a variety of agents which stimulate neurite extension also increase intracellular cyclic AMP. These agents included phospholipase A2 and phospholipase C. In an effort to clarify the relationship of the 'PI effect' to other NGF-induced events we investigated the effects of these agents and of cyclic AMP on phospholipid metabolism. All agents which elevate cyclic AMP stimulate phosphatidylinositol metabolism. In addition, elevated exogenous KCl, which does not stimulate cyclic AMP production, promotes neurite extension and also causes the 'PI effect'. These data suggest that an increase in the turnover of phosphatidylinositol may be a requisite event in neurite outgrowth. 相似文献
104.
Bilateral lesions of substantia nigra (SN) were evaluated for anticonvulsant effects in rats. Electrolytic and kainic acid lesions of SN reduced bicuculline-elicited seizure activity; lesions in the ventral midbrain tegmentum adjacent to SN were without an anticonvulsant effect. Lesions of SN also reduced the incidence and duration of tonic hindlimb extension in the maximal electroshock seizure test. Bilateral SN lesions appeared to decrease seizure susceptibility to a given stimulus intensity rather than altering the motor pattern of the seizures. Our results support the view that SN efferents constitute a critical gating mechanism in the propagation of seizure activity. 相似文献
105.
在戊巴比妥钠麻醉兔中,记录股动脉血压,心率(HR)和肾交感神经活动(RSNA)。在10分钟内股动脉放血使平均动脉压(MAP)下降至5.3 kPa,停止放血后让其自然恢复。重度失血过程中RSNA和HR呈现先兴奋后抑制的双相反应。迷走神经切断和静脉注射纳洛酮可翻转重度失血时RSNA的抑制,却不能阻断重度失血时HR的降低。延髓腹外侧头端(RVLM)注射γ一氨基丁酸(GABA)拮抗剂荷包牡丹碱和阿片肽拮抗剂纳洛酮均可翻转重度失血引起的RSNA抑制和HR下降。失血初期RSNA增强和心率(HR)增加不受迷走神经切断、静脉和RVLM注射纳洛酮和RVLM注射荷包牡丹碱的影响。这些结果表明RVLM中的阿片肽和GABA参与重度失血引起的RSNA抑制和HR下降,但与失血初期的RSNA和HR的升高无关。 相似文献
106.
J. J. Chrobak T. C. Napier 《Journal of neural transmission (Vienna, Austria : 1996)》1993,93(2):123-143
Summary The principle output of the nucleus accumbens innervates the ventral pallidum and rostral substantia innominata. GABA and opioid peptides are among the neurotransmitter candidates for this projection. The goal of the present experiments was to delineate further the physiology and pharmacology of the accumbens projection to the ventral pallidum. The trans-synaptic responsiveness of ventral pallidal and rostral substantia innominata neurons to electrical stimulation of the nucleus accumbens was examined concurrently with the ability of microiontophoretically applied morphine (an opioid agonist), naloxone (an opioid antagonist) and bicuculline (a GABA antagonist) to modulate evoked responses. Accumbens stimulation altered the firing rate in 60% of the 132 neurons tested. Fifty-two percent of responding neurons exhibited simple excitations or inhibitions in response to accumbens stimulation, while 48% exhibited complex response sequences with two or more evoked components. Predominant responses consisted of a short latency (<10 ms) and short duration (10 ms) excitation (51 % of responding neurons) and an inhibition with a variable, onset latency and, duration (52% of responding neurons). Evoked responses often occurred within limited areas within the ventral pallidum suggesting that activation of descending afferents can influence discrete targets within the region. A large majority (>80%) of neurons evoked by accumbens stimulation also exhibited a current-dependent and naloxone-sensitive increase in spontaneous firing to microiontophoretically applied morphine. Morphine shortened the duration of the accumbens-evoked, short latency excitation and attenuated the magnitude of the long-latency inhibition. Evoked responses in the presence of morphine were opposite to those observed with naloxone, but similar to bicuculline. Thus, opioid receptor activation may be functionally antagonistic to GABAergic neurotransmission in the ventral pallidum. The prominence of accumbens-evoked and morphine-sensitive neurons within the ventral pallidum corroborates the density of accumbens and opioid input to this brain region, and demonstrates that opioids serve as an important influence on neuronal activity and information processing in the ventral-striatopallidal pathway. 相似文献
107.
Kinetic differences in GABA receptor binding following GABA and bicuculline methiodide pretreatment 总被引:1,自引:0,他引:1
The kinetics of [3H]GABA binding were studied in cortical membranes following GABA and bicuculline methiodide (BCM) pretreatment at 37 degrees C. The slower parts of the biphasic ON and OFF rates can be attributed to the high affinity sites. BCM pretreatment decreased the ON and OFF rates of [3H]GABA binding, including the rapid initial ON- and OFF-phases. Decreased association rates of GABA were independent of GABA and concentration and suggested a rate determining dissociation of bound BCM (t1/2 = 35 min). 相似文献
108.
Morphologically, a GABAergic connection between the medial terminal nucleus of the accessory optic system and the nucleus of the optic tract, two primary visual nuclei involved in the optokinetic reflex, has been demonstrated. In this study it was investigated if the medial terminal nucleus forms an inhibitory input to movement direction selective units in the nucleus of the optic tract. Neurons in the nucleus of the optic tract were visually stimulated with moving large random square patterns in their preferred and non-preferred direction, and their activity was recorded extracellularly. Concomitantly, bipolar electrical stimulation was applied to the medial terminal nucleus and its effect was studied on the visual responses of units in the nucleus of the optic tract. Units in the nucleus of the optic tract were strongly inhibited during electrical stimulation of the medial terminal nucleus. The role of GABA in mediating this inhibition was investigated by applying bicuculline, a GABAA receptor antagonist, iontophoretically to the recorded units in the nucleus of the optic tract. However, although average spike rate levels of units in the nucleus of the optic tract increased with bicuculline, bicuculline did not reduce inhibition invoked by electrical stimulation of the medial terminal nucleus. A possible explanation for this observation is that this inhibition is GABAB receptor mediated. 相似文献
109.
目的 分析吸入麻醉药乙醚、安氟醚、异氟烷和七氟醚催眠作用与GABAA 受体的关系。方法 给小鼠分别腹腔注射麻醉剂量的乙醚、安氟醚、异氟烷、七氟醚 ,待小鼠翻正反射消失后 1min ,静脉注射一叶秋碱 5mg/kg或侧脑室注射荷包牡丹碱每只 0 .5μg /10 μl,对照组分别注射同等容积的生理盐水或人工脑脊液 ,观察并记录各组的翻正反射消失持续时间。结果 一叶秋碱和荷包牡丹碱对上述 4种麻醉药的翻正反射消失持续时间均无明显影响 (P >0 .0 5)。结论 GABAA 受体并非乙醚、安氟醚、异氟烷和七氟醚催眠作用的主要靶位 相似文献
110.
The convulsant compounds bicuculline (BICUC) and penicillin (PCN) are antagonists of GABA-mediated synaptic inhibition. In addition, we have shown that BICUC and PCN produced membrane depolarization of mouse spinal cord neurons in primary dissociated cell culture by blocking a potassium conductance, a non-synaptic direct effect. Both compounds also prolonged calcium-dependent action potentials of mouse dorsal root ganglion and spinal cord neurons in cell culture. Thus, BICUC and PCN had both synaptic and non-synaptic actions. The possibility that both synaptic and non-synaptic actions of BICUC and PCN are involved in their convulsant mechanism of action is discussed. 相似文献