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991.
Vila M Périer C Féger J Yelnik J Faucheux B Ruberg M Raisman-Vozari R Agid Y Hirsch EC 《The European journal of neuroscience》2000,12(1):337-344
Cellular expression of cytochrome oxidase subunit I (COI) mRNA has recently been used as a metabolic marker for neuronal activity to study the functional changes in the subthalamic nucleus (STN) in parkinsonism. The previous experimental studies have been performed when the pathological state was stabilized at a maximal level. In order to determine the evolution of changes in neuronal activity in the STN after nigrostriatal denervation, we analysed by in situ hybridization the cellular expression of COI mRNA in the subthalamic neurons at different times, from 6 h to 14 days, after unilateral intranigral microinjection of 6-hydroxydopamine (6-OHDA) in rats. In parallel, the time-dependent changes of the unit neuronal activity of subthalamic neurons have been recorded. Levels of COI mRNA increased by 41% in subthalamic neurons from 24 h after 6-OHDA intoxication, to 14 days (+26%). Similarly, electrical activity started to increase slightly 24 h after lesion (+20%) and remained significantly higher at 14 days after the lesion (+189%). Changes in neuronal mean discharge rate were associated with changes in the pattern of spiking activity, from a regular firing pattern to an irregular one with a high bursting activity. These results show that: (i) the hyperactivity of the STN represents a very early phenomenon in the physiopathology of parkinsonian syndromes; and (ii) that changes in COI mRNA expression slightly precede changes in electrical neuronal activity. 相似文献
992.
993.
Bailey AR von Engelhardt N Von Englehardt N Leng G Smith RG Dickson SL 《Journal of neuroendocrinology》2000,12(3):191-197
Noradrenergic systems are integrally involved in the release of growth hormone (GH) from the anterior pituitary gland and in regulating the activity of hypothalamic growth hormone-releasing hormone (GHRH) neurones. GH secretagogues act at both the pituitary and the hypothalamus to facilitate the release of GH. In male rats, using the induction of Fos protein as an indicator of neuronal activation, we examined whether neurones in the brainstem, the main noradrenergic input to the hypothalamus, were activated by systemic administration of peptide and non-peptide GH secretagogues. In addition, we examined the effects of chronic central noradrenaline depletion upon GH secretagogue-induced activation of the arcuate nucleus. Systemic injection of the GH secretagogues, GHRP-6 and MK-0677 induced Fos protein expression in a population of area postrema cells, but less than 10% of these cells were noradrenergic. Depletion of hypothalamic noradrenaline by the specific neurotoxin, 5-ADMP, did not alter GH secretagogue-induced activation of Fos protein in the arcuate nucleus compared to vehicle-treated controls. We conclude that the central actions of GH secretagogues involve the activation of non-noradrenergic cells in the area postrema and that GH secretagogue-induced activation of the arcuate nucleus occurs independently of noradrenergic tone. 相似文献
994.
Previous results suggest that norepinephrine decreases growth hormone (GH) release in goldfish by means of alpha-2 adrenoceptor activation. The intracellular mechanisms by which norepinephrine inhibits GH release were examined in the present study using dispersed goldfish pituitary cells. In 2-h static incubation experiments, norepinephrine and the alpha-2 agonist clonidine decreased basal GH release and the GH responses to stimulation by the dopamine D1 agonist SKF38393 and two native gonadotropin-releasing hormones (GnRH). Norepinephrine also reduced GH responses to the adenylate cyclase activator forskolin, two protein kinase C (PKC) activators (phorbol ester and synthetic diacylglycerol), and two Ca2+ ionophores (ionomycin and A23187). Similarly, norepinephrine applied as a 1-h pulse in cell column perifusion experiments reduced basal GH release and abolished the GH response to a 5-min pulse of arachidonic acid. In goldfish, D1-stimulated GH release is mediated by AC-, arachidonic acid-and Ca2+-dependent pathways, whereas GnRH action is coupled to PKC-and Ca2+-dependent mechanisms. These results suggest that norepinephrine activation of alpha-2 receptors inhibits ligand-induced GH secretion by actions subsequent to activation of these second messenger cascades. To further characterize norepinephrine mechanisms of action on unstimulated hormone release, the ability of norepinephrine and an alpha-2 agonist to affect activation of two second messenger cascades under basal conditions was also investigated. Static incubation with clonidine reduced cAMP production in a time-and dose-dependent manner, suggesting that norepinephrine inhibitory action can also be expressed at the level of cAMP production. Resting intracellular free calcium levels in single, identified goldfish somatotropes was unaffected by norepinephrine. However, the inhibitory effects of norepinephrine on basal GH secretion was not observed in the presence of a voltage-sensitive Ca2+ channel agonist. Whether these channels are targets for norepinephrine action on unstimulated GH release requires further investigation. 相似文献
995.
Williams B Bence M Everest H Forrest-Owen W Lightman SL McArdle CA 《Journal of neuroendocrinology》2000,12(2):159-166
gamma-amino butyric acid (GABA) is the major inhibitory neurotransmitter in the CNS, mediating fast inhibitory synaptic transmission, by activating GABAA receptors. However, these GABA-gated Cl- channels can also be excitatory, causing depolarization, and increasing Ca2+ entry via voltage-operated Ca2+ channels (VOCCs). Evidence exists for excitatory ionotropic GABA receptors in anterior pituitary cells, including gonadotropes, but these have not been directly characterized and their pharmacology remains controversial. Here we have measured the cytosolic Ca2+ concentration ([Ca2+]i) in alphaT3-1 gonadotropes, to test for expression of excitatory GABA receptors. The GABAA agonists, GABA and muscimol, both caused rapid, robust and dose-dependent increases in [Ca2+]i (EC50 values 2.7 and 1 microM), whereas the GABAB agonist, baclofen, did not. The GABAA antagonist, bicuculline, inhibited muscimol's effect, whereas the GABAB antagonist, phaclofen, did not. The neuroactive steroid 5alpha-pregnan-3alpha-ol-11,20-dione (an allosteric activator of GABAA receptors) increased [Ca2+]i, and this effect, like that of muscimol, was inhibited by picrotoxin. The muscimol effect on [Ca2+]i was blocked by the VOCC antagonist, nifedipine, or by Ca2+-free medium. When cells were pretreated with muscimol this increased the spike phase of the [Ca2+]i response to subsequent stimulation with gonadotropin-releasing hormone (GnRH). Similar amplification was seen in muscimol-pretreated cells stimulated with GnRH in Ca2+-free medium, but not when cells were pretreated with muscimol in Ca2+-free medium. The amplification was not, however, GnRH receptor-specific, because the spike response to ionomycin was also increased by muscimol pretreatment. These data provide the first direct evidence for expression of excitatory GABAA receptors, and the first demonstration of acute steroid effects, on GnRH-responsive pituitary cells. They also reveal a novel mechanism by which GABAA activation modulates GnRH action, raising the possibility that this may also influence gonadotrophin secretion from non-immortalized gonadotropes. 相似文献
996.
Uesugi H Shimizu H Maehara T Arai N Nakayama H 《Psychiatry and clinical neurosciences》2000,54(5):589-593
We investigated the presence of human herpesvirus 6 (HHV-6) and herpes simplex virus (HSV) in surgical tissue from temporal lobe epileptic patients. A total of 17 cases were studied, including eight males and nine females. The mean age was 24.9 +/- 11.1 years and the mean age of onset was 11.1 +/- 5.4 years. Five patients were diagnosed as encephalitis/meningitis and another three had a history of suspected encephalitis/meningitis, but no patient showed any obvious neurological symptom or mental handicap. Mesial and lateral temporal tissues were examined by polymerase chain reaction. Among six patients positive for HHV-6 (35%), the mesial temporal lobe was positive in four and the lateral temporal lobe was positive in three. Herpes simplex virus was positive in only one patient. Three of the six patients positive for HHV-6 did not show any apparent causes. Mild encephalitis/meningitis induced by HHV-6, a condition sometimes not recognized as encephalitis/meningitis, may be one of the most frequent causes of temporal lobe epilepsy. 相似文献
997.
川芎嗪及其衍生物对羟自由基的清除作用 总被引:29,自引:0,他引:29
目的:探讨川芎嗪及其衍生物对羟自由基的清除作用。方法:应用Fenton反应检测并计算50%羟自由基被清除时的药物浓度(EC_(50))。结果:结果显示对羟自由基均有明显清除作用,且呈剂量依赖关系。川芎嗪及其衍生物与苯甲酸和甘露醇的清除作用差异有极显著性(P<0.01),而相互间作用无明显差异(P>0.05)。结论:川芎嗪及其衍生物对羟自由基有明显的清除作用。 相似文献
998.
目的:探讨多药耐药集团(MDR1)在小细胞肺癌化疗中的作用和地位,方法:采用逆转录-多聚酶链式反应技术(RT/PCR)和免疫细胞化学染色法,检测了32例(初治原发癌21例和复治转移癌11例)小细胞肺癌患者血液中的MDR1mRNA水平和多药耐药蛋白(P-170)的表达,并对两种方法进行了比较。结果:初治的原发癌MDR1基因阳性表达率为14.29%,P-170蛋白阳性表达为14.27%,复治转移癌的MDR1基因阳性表达率为72.73%,P-170蛋白阳性表达为63.64%(P<0.01),有显著性差异。MDR1的基因和蛋白两种而检测方法具有一定的一致性,以RT/PTR方法具有更强的敏感性,结论:复治转移癌组比初治组具有更普遍的抗药性,且主要是获得性抗药,MDR1基因表达可作为临床合理地制定化疗方案,预测化疗效果的重要参考指标。 相似文献
999.
1000.
目的:观察纯中药制剂银康颗粒剂治疗银屑病的,临床疗效及治疗前后患者血粘度的变化。方法:将382例患者随机分为2组,治疗组252例应用银康颗粒剂治疗,对照组130例应用复方青黛胶囊治疗;对治疗组部分病例(212例)治疗前后血粘度指标进行观察。结果:治疗组治愈148例,好转82例,未愈22例,总有效率为91.12%;对照组治愈51例,好转46例,未愈33例,总有效率为74.62%,2组总有效率比较,差异有非常显著性意义(P<0.01)。治疗组患者治疗前后全血粘度差异无显著性意义(P>0.05),血浆粘度差异有显著性意义(P<0.05)。结论:风邪外袭、血虚生风、气滞血瘀是致病的主要原因。治疗应以清热祛风与养血活血并举。 相似文献