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991.
The perinatal period of brain is characterized by dynamic changes in structure and high propensity for epilepsy. Animal models have shown that alterations of AMPA receptor (AMPAR) assembly or function may be related to seizure-induced cell damage, long-lasting impairments in brain development and seizure threshold. However, effects of earlier epileptiform discharges on AMPAR composition and sub-cellular distribution remain understudied. In this study, we analyzed age-dependent variation of relative GluR1 and GluR2 protein levels in primary cultured rat cortical neurons at 7 DIV, 12 DIV, 17 DIV and 21 DIV. By inducing a single event of epileptiform activity at 6 DIV, we tested the effects of early-life seizure-like insults on AMPAR subunit distribution. We found a significant increase in synaptosomal membrane GluR1 expression in magnesium-free (MGF) medium-treated neurons at each time point detected (p < 0.05), while GluR2 expression increased at 7 DIV, and declined at 17 DIV and 21 DIV respectively (p < 0.05). That is, a trend of high GluR1 with much lower GluR2 expression on the surface membrane of epileptiform discharges experienced neurons over time in culture was presented. These findings in an in vitro model of early-life seizure may inform rodent models of epilepsy, as well as the cellular mechanism involved in epilepsy-associated brain dysfunction. 相似文献
992.
目的:检测宫内发育迟缓(IUGR)儿脐血胰岛素样生长因子-I(IGF-I)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平,分析这些指标的变化程度与胎儿期生长的关系。方法:将86例脐血标本分为IUGR(即小于胎龄儿)组和适于胎龄儿(AGA)组。采用放射免疫分析(RIA)测定IGF-I水平,免疫放射分析(IR-MA)测定IGFBP-3水平。两组间比较用t检验,两变量之间的关系采用相关回归分析。结果:与AGA组相比,IUGR组脐血IGF-I和IGFBP-3水平显著降低(P均〈0.01);IGF-I、IGFBP-3均随胎龄及出生体重增加而增加(P均〈0.01);IGFBP-3与IGF-I呈正相关(P〈0.01)。结论:脐血IGF-I和IGFBP-3的含量可作为判断新生儿生长发育程度的一项客观指标。 相似文献
993.
William B. Dobyns Ghayda M. Mirzaa 《American journal of medical genetics. Part C, Seminars in medical genetics》2019,181(4):582-590
Megalencephaly (MEG) is a developmental abnormality of brain growth characterized by early onset, often progressive, brain overgrowth. Focal forms of megalencephaly associated with cortical dysplasia, such as hemimegalencephaly and focal cortical dysplasia, are common causes of focal intractable epilepsy in children. The increasing use of high throughput sequencing methods, including high depth sequencing to more accurately detect and quantify mosaic mutations, has allowed us to identify the molecular etiologies of many MEG syndromes, including most notably the PI3K‐AKT‐MTOR related MEG disorders. Thorough molecular and clinical characterization of affected individuals further allow us to derive preliminary genotype–phenotype correlations depending on the gene, mutation, level of mosaicism, and tissue distribution. Our review of published data on these disorders so far shows that mildly activating variants (that are typically constitutional or germline) are associated with diffuse megalencephaly with intellectual disability and/or autism spectrum disorder; moderately activating variants (that are typically high‐level mosaic) are associated with megalencephaly with pigmentary abnormalities of the skin; and strongly activating variants (that are usually very low‐level mosaic) are associated with focal brain malformations including hemimegalencephaly and focal cortical dysplasia. Accurate molecular diagnosis of these disorders is undoubtedly crucial to more optimally treat children with these disorders using PI3K‐AKT–MTOR pathway inhibitors. 相似文献
994.
目的 探讨KCNN3基因1137~1140的4个碱基缺失所致移码突变与精神分裂症的关系。方法 95个核心家系共289名家庭成员,包含107例精神分裂症患者纳入本研究。精神分裂症采用CCMD-Ⅱ-R诊断标准。KCNN3基因1137~1140的4个碱基缺失基因型检测使用PCR技术和限制性内切酶DdeI消化方法。精神分裂症与KCNN3基因1137~1140缺失4个碱基的关联分析采用基于单倍型的单倍型相对风险率和传递/不平衡检验。结果 患者组与正常父母组比较,KCNN3基因1137~1140的4个碱基缺失的基因型频数和等位基因频率分布差异无统计学意义(χ^2=0.253,P〉0.05和χ^2=0.010,P〉0.05)。基于单倍型的单倍型相对风险分析发现父母传递与不传递给患者的KCNN3基因等位基因之间差异无统计学意义(χ^2=0.042,P〉0.05)。传递不平衡检验结果发现KCNN3基因等位基因传递不存在连锁不平衡(χ^2=3.000,P=0.0833)。结论 本组研究对象中,KCNN3基因第1外显子1137~1140的4个碱基缺失的发生率少;分析结果提示KCNN3基因第1外显子1137~1140的4个碱基缺失的等位基因与精神分裂症无关联。 相似文献
995.
Barr IG Komadina N Hurt AC Iannello P Tomasov C Shaw R Durrant C Sjogren H Hampson AW 《Journal of medical virology》2005,76(3):391-397
During 2003, Australia and New Zealand experienced substantial outbreaks of influenza. The strain responsible was an A(H3N2) influenza virus described as A/Fujian/411/2002-like, which had circulated as a minor variant in the previous Northern Hemisphere (NH) winter, mainly in Korea and Japan. Early in the year the isolates were very similar to those that had been previously isolated in the NH, however, a reassortant strain emerged early in the New Zealand winter, followed by the appearance of similar viruses in Australia and other regional areas. While the hemagglutinin HA1 sequence of these viruses demonstrated only minor differences from the A/Fujian/411/2002 reference strain, the neuraminidase gene was clearly different from that of other recently circulating H3 viruses and most closely matched an earlier reference strain A/Chile/6416/2001. Three internal genes (NS, NP, M) in the reassortant viruses were also more closely related to the A/Chile/6416/2001 lineage. This reassortant A(H3) virus predominated in Australia and New Zealand in 2003 was also seen in Brazil and Malaysia during 2003 and was widespread in the United States and Europe during their 2003-04 winter. Interestingly most of the strains of A(H3) that were isolated at the beginning of the 2004 winter in Australia, did not have this earlier A/Chile/6416/2001-like neuraminidase but had a neuraminidase that was similar to that of the reference strain A/Fujian/411/2002. This was suggestive of the re-introduction of influenza A(H3) from other countries, however, there was still low level circulation of the reassortant virus in 2004 with isolates detected in Australia and Singapore. 相似文献
996.
《Immunity》2021,54(11):2481-2496.e6
997.
Pernollet M Jouvin-Marche E Leroy V Vigan I Zarski JP Marche PN 《Clinical and experimental immunology》2002,130(3):518-525
Intrahepatic lymphocytes are believed to be involved in the immunopathogenesis of hepatitis C virus (HCV) infection and the evolution of HCV-induced hepatitis. In the present study, we examined the three main intrahepatic lymphocyte subsets, namely CD3+CD56- conventional T lymphocytes, CD3+CD56+ natural T (NT) lymphocytes and CD3-CD56+ natural killer (NK) lymphocytes in HCV-infected patients. The proportion of each lymphocyte subset was evaluated both in liver biopsies and in samples of peripheral blood lymphocytes (PBL) by flow cytometry in 21 patients with histologically proven chronic hepatitis C. Simultaneously, alanine aminotransferase (ALT) levels, viral load and histological lesions were assessed. Neither NT nor NK populations correlated with any biochemical, viral or histological parameters. Furthermore, Valpha24+ NT lymphocytes showed no preferential enrichment in the liver of HCV-infected patients. Regarding conventional T lymphocytes, a highly significant linear correlation was found between intrahepatic CD3+CD56- T lymphocytes and the Knodell score, a numerical score for assessing histological activity and fibrosis (r = 0.715, P < 0.0001) and more specifically with the periportal necrosis parameter, which is the main lesion of chronic hepatitis C. In addition, analysis of the peripheral compartment revealed a high correlation between values of CD3+CD56- lymphocytes and both Knodell score (r = 0.624, P = 0.003) and serum ALT levels and again with periportal necrosis. The strong correlation between the proportion of peripheral CD3+CD56- conventional T lymphocytes and the severity of hepatic lesions leads us to propose that evaluation of this accessible peripheral population could be used as an indicator test for the severity of histological lesions in chronic hepatitis C. Abbreviations: 相似文献
998.
Sodium fusidate ameliorates the course of diabetes induced in mice by multiple low doses of streptozotocin 总被引:6,自引:0,他引:6
Nicoletti F Di Marco R Conget I Gomis R Edwards C Papaccio G Bendtzen K Sandler S 《Journal of autoimmunity》2000,15(4):395-405
We studied the effects of the immunosuppressant sodium fusidate (fusidin) on murine immunoinflammatory diabetes mellitus (DM) induced by multiple low doses of streptozotocin (SZ). Fusidin was given by gavage to three strains of mice (C57KsJ, C57BL/6, CD1) at doses 10 or 100 mg/kg body weight every other day. The drug was administered as an early or late prophylactic regime starting either 1 day prior to the first or after the fifth and last injection of SZ. In both situations the largest dose of fusidin successfully reduced the clinical, chemical and histological signs of DM, the treated mice having significantly lower glycaemic values and milder (often absent) insulitis compared with sham-treated animals or controls given SZ alone. The antidiabetogenic effect was long-lasting as it was maintained up to 1 month after cessation of therapy. In contrast, fusidin prophylaxis failed to prevent development of hyperglycaemia acutely induced by one single and high (160 mg/kg) dose of SZ, which is a model of DM primarily due to the toxic action of SZ on the beta cells and does not involve immunopathogenetic mechanisms.On day 14 after SZ, fusidin markedly altered the circulating cytokine profile induced in vivo by ConA, reducing the levels of IFN-gamma, IL-2 and TNF-alpha and augmenting the level of IL-6. However, only the inhibitory effect of the drug on the synthesis/release of IFN-gamma seemed to be causally related to its capacity to counteract the SZ-induced DM. In fact, the disease was prevented by a neutralizing monoclonal antibody (mAb) against IFN-gamma, but not by anti-IL-2 receptor mAb, a soluble form of TNF-receptor type 1 or recombinant human IL-6. The prevention of disease by fusidin was also partly reversed by exogenously administered recombinant mouse IFN-gamma.The data provide further in-vivo evidence for the anti-diabetogenic and immunomodulatory properties of fusidin and indicate that this drug could have a role in prevention and treatment of human type 1 DM. 相似文献
999.
In cat hypoglossal motoneurons after axotomy the synaptic efficacy of inhibitory synapses made by the lingual nerve afferent fibers was studied. The amplitude of the short- and the long-lasting inhibitory postsynaptic potential produced in tongue protruder motoneurons 24 days after axotomy by stimulation of the lingual nerve was significantly reduced in size as compared with the control on the unoperated side. In most protruder motoneurons 40 days after axotomy a large excitatory postsynaptic potential and a spike was produced by stimulation of either the ipsilateral or the contralateral lingual nerve. We have demonstrated that the decline of synaptic efficacy of inhibitory synapses for the short-lasting inhibitory postsynaptic potential was more prominent than that for the long-lasting inhibitory potential in the motoneuron 24 days after axotomy. After the cut axons of protruder motoneurons were re-united to tongue muscles, we have demonstrated that the decline of synaptic efficacy of inhibitory synapses for the short-lasting inhibitory postsynaptic potential was less prominent than that in axotomized protruder motoneurons. 相似文献
1000.
目的:研究FoxP3(Forkhead Box P3)基因在小鼠T细胞的表达情况,以及重组FoxP3腺相关病毒(adeno-associatedvirus,AAV)对小鼠CD4^+CD25^-T细胞功能的影响。方法:采用实时定量PCR检测CD4^+CD25^-T细胞和CD4^+CD25^-T细胞FoxP3 mRNA表达情况,利用基因重组技术构建FoxP3腺相关病毒载体,体外转染CD4^+CD25^-T细胞,通过细胞增殖试验观察转染CD4^+CD25^-T细胞功能变化。结果:CD4^+CD25^-T细胞较CD4^+CD25^-T相比高水平表达FoxP3基因mRNA,重组FoxP3腺相关病毒转染后的CD4^+CD25^-T细胞对CD3单抗的刺激呈低反应性,并且能抑制新鲜分离CD4^+CD25^-T细胞的增殖。结论:FoxP3基因转染的CD4^+CD25^-T细胞在体外具有抑制T细胞活化增殖的功能。 相似文献