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61.
62.
C Hernández E Santamatilde KJ McCreath AM Cervera I Díez D Ortiz-Masiá N Martínez S Calatayud JV Esplugues MD Barrachina 《British journal of pharmacology》2009,156(2):262-272
Background and purpose:
Mucosal microcirculation is compromised during gastric damage induced by non-steroidal anti-inflammatory drugs, such as aspirin. Consequently, oxygen supply to epithelial cells is decreased. The trefoil factor (TFF) peptides are involved in mechanisms of defence and repair in the gastrointestinal tract but their regulation at sites of gastric injury is unknown.Experimental approach:
Hypoxia and expression of TFF genes and peptides were measured in the damaged stomach of aspirin-treated rats. In a human gastric cell line (AGS cells), the effects of hypoxia and of hypoxia inducible factor (HIF)-1 (through transient transfection of HIF-1α siRNA or over-expression of HIF-1α) on TFF gene expression were evaluated.Key results:
Hypoxyprobe immunostaining, up-regulation of TFF2 (1.9-fold) and TFF3 (1.8-fold) and a non-significant increase of TFF1 (1.5-fold) mRNA were observed in the damaged stomach of aspirin-treated rats, compared with control animals. Hypoxia (3% O2, 16 h) induced mRNA for TFF1 (5.8-fold), TTF2 (9.1-fold) and TFF3 (9.3-fold) in AGS cells, an effect mediated by HIF-1, as transient transfection of HIF-1α siRNA reduced the effects of hypoxia. Over-expression of HIF-1α by transfection in non-hypoxic epithelial cells produced a similar pattern of TFF induction to that observed with hypoxia and transactivated a TFF1 reporter construct.Conclusions and implications:
Hypoxia inducible factor-1 mediated the induction of TFF gene expression by hypoxia in gastric epithelial cells. Low oxygen levels and up-regulation of TFF gene expression in the damaged stomach of aspirin-treated rats suggest that hypoxia induced expression of TFF genes at sites of gastric injury. 相似文献63.
N Apostolova LJ Gomez-Sucerquia A Moran A Alvarez A Blas-Garcia JV Esplugues 《British journal of pharmacology》2010,160(8):2069-2084
BACKGROUND AND PURPOSE
Efavirenz (EFV) is widely used in the treatment of HIV-1 infection. Though highly efficient, there is growing concern about EFV-related side effects, the molecular basis of which remains elusive.EXPERIMENTAL APPROACH
In vitro studies were performed to address the effect of clinically relevant concentrations of EFV (10, 25 and 50 µM) on human hepatic cells.KEY RESULTS
Cellular proliferation and viability were reduced in a concentration-dependent manner. Analyses of the cell cycle and several cell death parameters (chromatin condensation, phosphatidylserine exteriorization, mitochondrial proapoptotic protein translocation and caspase activation) revealed that EFV triggered apoptosis via the intrinsic pathway. In addition, EFV directly affected mitochondrial function in a reversible manner, inducing a decrease in mitochondrial membrane potential and an increase in mitochondrial superoxide production, followed by a reduction in cellular glutathione content. The rapidity of these actions rules out any involvement of mitochondrial DNA replication, which, until now, was thought to be the main mechanism of mitochondrial toxicity of antiretroviral drugs. Importantly, we also observed an increase in mitochondrial mass, manifested as an elevated cardiolipin content and enhanced expression of mitochondrial proteins, which was not paralleled by an increase in the mtDNA/nuclear DNA copy number ratio. The toxic effect of EFV was partially reversed by antioxidant pretreatment, which suggests ROS generation is involved in this effect.CONCLUSION AND IMPLICATIONS
Clinically relevant concentrations of EFV were shown to be mitotoxic in human hepatic cells in vitro, which may be pertinent to the understanding of the hepatotoxicity associated with this drug. 相似文献64.
体重部分地受大脑或胃肠道合成的肽类激素的调控。Ghrelin前激素原含117个氨基酸残基,经翻译后裂解作用形成Ghrelin,由28个氨基酸组成。我们检索基因库,与另外11种哺乳动物进行Ghrelin前激素原的序列比较,除了已知的Ghrelin信号肽,我们还确定了另一保守区,侧链含有转化酶裂解部位,编码一种23个氨基酸的肽链,其C端侧翼有保守的甘氨酸残基,可能经酰胺化作用。我们称此Ghrelin相关肽为肥胖抑素(Obestatin)。 相似文献
65.
66.
We measured ascorbic acid (reduced and oxidized) in brain, CSF and blood, before, during and after cerebral ischemia in newborn piglets. Bilateral carotid ligation induced a 54% decrease in cerebral blood flow (p < 0.01) and a 43% decrease in the cerebral metabolic rate of oxygen (p < 0.01). After ischemia and reperfusion, we obtained a 60% decrease (p < 0.01) in total brain ascorbic acid content. CSF ascorbic acid increased during reperfusion:+60% at 30min (p < 0.001) and +160% at 120min (p < 0.05). Blood ascorbic acid content did not change. These changes and the absence of massive oxidation of ascorbic acid in brain tissue suggest release of ascorbic acid by the brain during ischemia. 相似文献
67.
Kaaijk EM; Beek JF; Hamerlynck JV; van der Veen F 《Human reproduction (Oxford, England)》1997,12(11):2370-2372
We performed unilateral oophorectomy (UO) in three patients with polycystic
ovary syndrome (PCOS) and long-standing infertility. The indication for
performing this procedure was a combination of ovarian pathology and the
long-standing infertility. All three patients were resistant to clomiphene
citrate and before UO all patients had been treated unsuccessfully with
gonadotrophins and in-vitro fertilization. All three patients became
ovulatory within the first month after UO. Two patients conceived 11 and 12
months after surgery respectively and delivered healthy babies.
Testosterone concentrations decreased in two patients to upper values of
the normal range and remained unchanged in one patient. We conclude that
restoration of ovulation can be a beneficial side-effect of UO in
clomiphene citrate resistant patients with PCOS and long-standing
infertility.
相似文献
68.
Isolated left thoracic isomerism 总被引:2,自引:0,他引:2
69.
TGF-β2对树突状细胞表型和功能的影响 总被引:3,自引:1,他引:2
目的: 研究转化生长因子-β2 (TGF-β2)对树突状细胞(dendritic cells, DC)表型和功能的影响. 方法: 体外培养骨髓来源的DC(BMDC)及TGF-β2诱导的DC(TGFβ2-DC). 采用双色免疫荧光化学染色或流式细胞仪(FCM)分析DC的细胞表型. 分离纯化脾脏来源的同种异体T细胞和CD4+ T细胞. 用BMDC及TGFβ2-DC刺激T细胞增殖,并用混合淋巴细胞反应(MLR)测定其能力. 在CD4+ T细胞与BMDC或TGFβ2-DC共培养5 d后,用FCM检测CD4+ T细胞表型的变化. 结果: BMDC表现为CD11c, CD86, MHC class II+和CD8а-的髓系DC. TGF-β2的诱导抑制了DC表面协同刺激分子、MHC classII的表达(P<0.01),并抑制其刺激同种异体T细胞增殖的能力. 与BMDC诱导的CD4+ T细胞相比,TGFβ2-DC诱导的CD4+ T细胞CD152(细胞毒T淋巴细胞相关分子4, CTLA-4)表达上升(P<0.01). 结论: TGF-β2的诱导促使DC表面协同刺激因子表达下降,T细胞合成CTLA-4增加,T细胞的活化和增殖受到明显抑制. 相似文献
70.