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1.
《Biochemical pharmacology》2015,98(4):439-444
Nicotinic acetylcholine receptors (nAChRs) are expressed widely in the CNS, and mediate both synaptic and perisynaptic activities of endogenous cholinergic inputs and pharmacological actions of exogenous compounds (e.g., nicotine and choline). Behavioral studies indicate that nicotine improves such cognitive functions as learning and memory, however the cellular mechanism of these actions remains elusive. With help from newly developed biosensors and optogenetic tools, recent studies provide new insights on signaling mechanisms involved in the activation of nAChRs. Here we will review α7 nAChR’s action in the tri-synaptic pathway in the hippocampus. The effects of α7 nAChR activation via either exogenous compounds or endogenous cholinergic innervation are detailed for spontaneous and evoked glutamatergic synaptic transmission and synaptic plasticity, as well as the underlying signaling mechanisms. In summary, α7 nAChRs trigger intracellular calcium rise and calcium-dependent signaling pathways to enhance glutamate release and induce glutamatergic synaptic plasticity. 相似文献
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《Saudi Dental Journal》2022,34(7):565-571
PurposeThis study aimed to evaluate the neuroprotective ability of the conditioned medium of stem cells from human exfoliated deciduous teeth (CM-SHED) to prevent glutamate-induced apoptosis of neural progenitors.Materials and methodsNeural progenitors were isolated from two-day-old rat brains, and the conditioned medium was obtained from a mesenchymal stem cell SHED. Four groups were examined: neural progenitor cells cultured in neurobasal medium with (N + ) and without (N-) glutamate and glycine, and neural progenitor cells cultured in CM-SHED with (K + ) and without (K-) glutamate and glycine.ResultsThe expression of GABA A1 receptor (GABAAR1) messenger RNA (mRNA) in neural progenitor measured by real-time quantitative PCR. GABA contents were measured by enzyme-linked immunosorbent assay, whereas the apoptosis markers caspase-3 and 7-aminoactinomycin D were analysed with a Muse® cell analyzer. The viability of neural progenitor cells in the K + group (78.05 %) was higher than the control group N- (73.22 %) and lower in the N + group (68.90 %) than in the control group. The K + group showed the highest GABA content, which significantly differed from that in the other groups, whereas the lowest content was observed in the N + group. The expression level of GABAAR1 mRNA in the K + group was the highest compared to that in the other groups. CM-SHED potently protected the neural progenitors from apoptosis.ConclusionsCM-SHED may effectively prevent glutamate-induced apoptosis of neural progenitors. 相似文献
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The present study investigated the effect of prostaglandin (PG) E2 and PGI2 on intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1β (IL-1β)-stimulated human gingival fibroblasts (HGF). IL-1β potently induced ICAM-1 expression in HGF and indomethacin, a cyclooxygenase inhibitor, enhanced ICAM-1 expression in the cells. These data showed that endogenous PGs generated by HGF stimulated with IL-1β downregulated ICAM-1 expression. IL-1β significantly increased the levels of PGE2 and, to a lesser extent, those of 6-keto-PGF1α (a stable metabolite of PGI2 ) in the culture media of HGF. Indomethacin completely inhibited the production of PGE2 and 6-keto-PGF1α in IL-1β-stimulated HGF. Exogenous PGE2 and carbacyclin (a stable derivative of PGI2 ) in the presence of indomethacin dose-dependently suppressed ICAM-1 expression in IL-1β-challenged HGF. Since PGE2 and PGI2 are known to elevate intracellular cyclic AMP (cAMP) levels, we examined the effect of dibutyryl cAMP, a cAMP analogue, and isobutylmethylxanthine, a phosphodiesterase inhibitor, on ICAM-1 expression. Both agents downregulated ICAM-1 expression in IL-1β-stimulated HGF. These results suggest that PGE2 and PGI2 downregulate ICAM-1 expression in IL-1β-stimulated HGF through a cAMP-dependent mechanism and that intracellular cAMP elevation in HGF may control inflammatory and immune responses in periodontal disease. 相似文献
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This review discusses the current understanding of biomarkers of immune quiescence based on reviews of published literature in kidney transplant operational tolerance and mechanistic studies based on a better characterization of the stable, well-functioning renal allograft. 相似文献
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Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons. 相似文献
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支气管哮喘是临床常见的气道慢性炎症性疾病,以气道高反应性、慢性气道炎症和气道重塑为病理生理特征,其发病机制目前尚未完全阐明。环磷酸腺苷(cAMP)是体内重要的第二信使,参与调控机体新陈代谢、细胞钙信号传导、细胞生长与分化、凋亡等多种病理生理过程。长期以来,蛋白激酶A (PKA)被认为是介导cAMP生物学效应的唯一下游信号分子。但新近发现的新型cAMP靶分子——cAMP直接激活的交换蛋白(Epac)的发现打破了这一说法。大量研究证实,Epac可单独或协同PKA介导cAMP的多种生物学效应。本文就Epac在支气管哮喘发病中的作用及其可能机制作一综述,为寻找哮喘治疗新靶点奠定基础。 相似文献
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目的观察六味地黄汤对2型糖尿病胰岛素抵抗大鼠环磷酸腺苷(c AMP)及脂肪组织磷酸二酯酶3B(PDE3B)的影响,探讨其改善2型糖尿病的作用机制。方法将80只SD大鼠随机分为空白组和造模组,造模组采用高脂高糖喂养加腹腔注射STZ造模。将成模大鼠分为模型组、罗格列酮组、六味地黄汤组。各给药组每日给予相应药物灌胃,模型组和空白组给予等量生理盐水,连续30 d。常规检测大鼠空腹血糖(FBG),ELISA检测大鼠血清c AMP和胰岛素(INS)水平,Western Blot检测脂肪组织PDE3B蛋白表达,实时荧光定量PCR检测脂肪组织PDE3B m RNA表达。结果与模型组比较,各给药组大鼠FBG、FINS水平降低(P0.05,P0.01);六味地黄汤组大鼠脂肪组织PDE3B蛋白及m RNA表达升高、血清c AMP浓度降低(P0.01)。结论六味地黄汤可上调脂肪组织PDE3B因子表达,降低c AMP浓度,这可能是其改善2型糖尿病大鼠胰岛素抵抗的作用机制之一。 相似文献
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本文用放免法测定了38例正常儿及47例 ITP 患儿血小板内 cAMP 值。发现无论急、慢性患儿血小板内 cAMP 值均显著增高,其增高与血小板功能呈负相关,与血小板计数无相关性。急性患儿 PAIgG 增高,血小板内 cAMP 亦增高,二者之间呈正相关,而慢性患儿则无此相关性。并对 cAMP 的增高与 ITP 的发病机制进行了阐述。 相似文献