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431.
Exercise training-induced improvements in insulin action 总被引:2,自引:0,他引:2
Individuals with insulin resistance are characterized by impaired insulin action on whole-body glucose uptake, in part due to impaired insulin-stimulated glucose uptake into skeletal muscle. A single bout of exercise increases skeletal muscle glucose uptake via an insulin-independent mechanism that bypasses the typical insulin signalling defects associated with these conditions. However, this 'insulin sensitizing' effect is short-lived and disappears after approximately 48 h. In contrast, repeated physical activity (i.e. exercise training) results in a persistent increase in insulin action in skeletal muscle from obese and insulin-resistant individuals. The molecular mechanism(s) for the enhanced glucose uptake with exercise training have been attributed to the increased expression and/or activity of key signalling proteins involved in the regulation of glucose uptake and metabolism in skeletal muscle. Evidence now suggests that the improvements in insulin sensitivity associated with exercise training are also related to changes in the expression and/or activity of proteins involved in insulin signal transduction in skeletal muscle such as the AMP-activated protein kinase (AMPK) and the protein kinase B (Akt) substrate AS160. In addition, increased lipid oxidation and/or turnover is likely to be another mechanism by which exercise improves insulin sensitivity: exercise training results in an increase in the oxidative capacity of skeletal muscle by up-regulating lipid oxidation and the expression of proteins involved in mitochondrial biogenesis. Determination of the underlying biological mechanisms that result from exercise training is essential in order to define the precise variations in physical activity that result in the most desired effects on targeted risk factors, and to aid in the development of such interventions. 相似文献
432.
Muscle contractures in patients with cerebral palsy and acquired brain injury are associated with extracellular matrix expansion,pro‐inflammatory gene expression,and reduced rRNA synthesis 下载免费PDF全文
433.
Peroxisomal biogenesis disorders are caused by disruption of long chain fatty acid metabolism due to mutations in PEX genes. Individuals with these disorders often have vision loss due to optic atrophy and pigmentary retinopathy. We report an unusual retinal manifestation of peroxisomal biogenesis disorder. 相似文献
434.
目的探讨中成药津力达颗粒对骨骼肌线粒体生物发生和胰岛素敏感性的影响。方法随机将雄性SD大鼠分为正常饲养组12只、高脂饲养组24只,6周后每组选取6只行高胰岛素-正葡萄糖钳夹试验,鉴定造模成功后,分别测定体重、胰岛素抵抗指数(HOMA-IR)、腹腔注射葡萄糖耐量实验(IPGTT)、葡萄糖输注率(GIR)等。余造模成功高脂喂养的18只大鼠进一步分为模型组、吡格列酮干预组、津力达颗粒干预组,继续喂养8周,分别测定体重、血脂、IPGTT、GIR等,并检测骨骼肌组织中Toll样受体2(TLR2)蛋白,以及线粒体生物发生指标过氧化物酶体增殖物激活受体γ共激活因子α(PGC1α)、线粒体融合蛋白2(MFN2)、核呼吸因子1(NRF-1)和胰岛素信号通路磷脂酰肌醇3激酶(PI3K)、磷酸化蛋白激酶B(P-AKT)、葡萄糖转运蛋白4(GLUT4)等蛋白的表达水平。结果①喂养6周后:与正常组相比,模型组体重、HOMA-IR均显著升高,IPGTT各时点血糖显著升高,GIR明显下降,差异均有统计学意义(P<0.05)。②喂养14周后:与模型组相比,吡格列酮干预组和津力达颗粒干预组大鼠体重及血脂水平明显下降,IPGTT各时点血糖显著下降,GIR显著升高,差异均有统计学意义(P<0.05)。③喂养14周后:与模型组相比,津力达颗粒干预组和吡格列酮干预组上调了线粒体生物发生指标PGC1α、MFN2、NRF-1以及胰岛素信号通路PI3K、P-AKT、GLUT4等蛋白表达水平,并且下调了骨骼肌组织中TLR2蛋白的表达,差异有统计学意义(P<0.05)。结论津力达颗粒与吡格列酮类似,可能通过促进骨骼肌线粒体生物发生而改善胰岛素敏感性。 相似文献
435.
Yoon Hee Kim Jae In Jung Young Eun Jeon So Mi Kim Su Hee Hong Tae Young Kim Eun Ji Kim 《Nutrition Research And Practice》2022,16(3):298
BACKGROUND/OBJECTIVESThe effectiveness of natural compounds in improving athletic ability has attracted attention in both sports and research. Gynostemma pentaphyllum (Thunb.) leaves are used to make traditional herbal medicines in Asia. The active components of G. pentaphyllum, dammarane saponins, or gypenosides, possess a range of biological activities. On the other hand, the anti-fatigue effects from G. pentaphyllum extract (GPE) and its effective compound, gypenoside L (GL), remain to be determined.MATERIALS/METHODSThis study examined the effects of GPE on fatigue and exercise performance in ICR mice. GPE was administered orally to mice for 6 weeks, with or without treadmill training. The biochemical analysis in serum, glycogen content, mRNA, and protein expressions of the liver and muscle were analyzed.RESULTSThe ExGPE (exercise with 300 mg/kg body weight/day of GPE) mice decreased the fat mass percentage significantly compared to the ExC mice, while the ExGPE showed the greatest lean mass percentage compared to the ExC group. The administration of GPE improved the exercise endurance and capacity in treadmill-trained mice, increased glucose and triglycerides, and decreased the serum creatine kinase and lactate levels after intensive exercise. The muscle glycogen levels were higher in the ExGPE group than the ExC group. GPE increased the level of mitochondrial biogenesis by enhancing the phosphorylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein and the mRNA expression of nuclear respiratory factor 1, mitochondrial DNA, peroxisome proliferator-activated receptor-δ, superoxide dismutase 2, and by decreasing the lactate dehydrogenase B level in the soleus muscle (SOL). GPE also improved PGC-1α activation in the SOL significantly through AMPK/p38 phosphorylation.CONCLUSIONSThese results showed that GPE supplementation enhances exercise performance and has anti-fatigue activity. In addition, the underlying molecular mechanism was elucidated. Therefore, GPE is a promising candidate for developing functional foods and enhancing the exercise capacity and anti-fatigue activity. 相似文献
436.
目的 观察肿瘤坏死因子α(TNF-α)对脂肪细胞线粒体生物合成和锌α2糖蛋白(ZAG)表达的影响.方法 体外培养3T3-L1前脂肪细胞并诱导分化为成熟脂肪细胞,分别以不同浓度TNF-α干预48 h.采用RT-PCR和Westem blot方法检测过氧化物酶增殖型受体γ辅助活化因子1 α(PGC-1 α),核呼吸因子1(NRF-1),核呼吸因子2(NRF-2),线粒体转录因子A(mtTFA)及锌α2糖蛋白(ZAG)mRNA和蛋白质表达;采用线粒体特异性染料Mito Traker Green预染成熟脂肪细胞,激光共聚焦显微镜下观察线粒体荧光强度.结果 TNF-α抑制脂肪细胞的ZAG及PGC-1 α、TFAM、NRF-1、NRF-2 mRNA和蛋白质的表达(P<0.05);TNF-α干预3T3-L1脂肪细胞的线粒体荧光强度低于对照组.结论 TNF-α减少脂肪细胞的线粒体生物合成及锌α2糖蛋白的mRNA和蛋白质表达. 相似文献
437.
Anna Bieber Cristina Capitanio Philipp S. Erdmann Fabian Fiedler Florian Beck Chia-Wei Lee Delong Li Gerhard Hummer Brenda A. Schulman Wolfgang Baumeister Florian Wilfling 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(39)
Autophagosomes are unique organelles that form de novo as double-membrane vesicles engulfing cytosolic material for destruction. Their biogenesis involves membrane transformations of distinctly shaped intermediates whose ultrastructure is poorly understood. Here, we combine cell biology, correlative cryo-electron tomography (cryo-ET), and extensive data analysis to reveal the step-by-step structural progression of autophagosome biogenesis at high resolution directly within yeast cells. The analysis uncovers an unexpectedly thin intermembrane distance that is dilated at the phagophore rim. Mapping of individual autophagic structures onto a timeline based on geometric features reveals a dynamical change of membrane shape and curvature in growing phagophores. Moreover, our tomograms show the organelle interactome of growing autophagosomes, highlighting a polar organization of contact sites between the phagophore and organelles, such as the vacuole and the endoplasmic reticulum (ER). Collectively, these findings have important implications for the contribution of different membrane sources during autophagy and for the forces shaping and driving phagophores toward closure without a templating cargo.Macroautophagy (autophagy hereafter) is a key pathway to maintain cellular homeostasis. In this process, a de novo synthesized double-membrane vesicle, the autophagosome, engulfs cellular material in response to stress conditions (1). This culminates in autophagosome fusion with lysosomes (or the vacuole in yeast) to remove and recycle its cargo. Fluorescence microscopy has identified the hierarchical order of the autophagy machinery during autophagosome biogenesis (2, 3). In addition, many of the membrane intermediates have been visualized at low resolution with conventional electron microscopy (4–7). These and other methods have revealed that autophagy proceeds in several steps: (I) membrane nucleation, (II) growth of the cup-shaped phagophore, (III) closure, and (IV) fusion of the autophagosome with the lytic compartment (8). Meanwhile, pioneering genetic and biochemical studies have revealed key regulators of autophagosome biogenesis (8, 9). In yeast, nitrogen starvation triggers the first step of phagophore nucleation through assembly of the molecular machinery in the pre-autophagosomal structure (PAS) next to the vacuole (10). The phagophore is initially formed by fusion of few vesicles carrying the transmembrane protein Atg9 (11–13). It then grows both by fusion of vesicles (e.g., Atg9 or COPII vesicles (14)) and by lipid transfer from the endoplasmic reticulum (ER) through protein complexes such as Atg2/Atg18 (15). Membrane expansion is further driven by conjugation of the ubiquitin-like protein Atg8 to phosphatidylethanolamine in the phagophore membrane (16). During growth, the initial membrane disk assumes a characteristic cup shape, a transition that is likely driven by the highly curved and therefore energetically unfavorable phagophore rim (17). After closure and maturation, the resulting autophagosome fuses with the vacuole, releasing the inner vesicle—now called “autophagic body”—for degradation.Despite the importance of autophagy and the efforts in deciphering the molecular machinery underlying it (8), it is still unknown how membranes are organized and transformed on an ultrastructural level during autophagosome biogenesis. In situ cryo-electron tomography (cryo-ET) can reveal membrane structures directly in their native cellular environment (18, 19). Yet monitoring the formation of an organelle poses the challenge to capture a rare event with many intermediates along the process. To overcome these hurdles, we combined several strategies to dissect the formation of autophagosomes using cryo-ET: (I) stimulating their formation to increase the abundance of all species involved, (II) using mutants that accumulate intermediates that are naturally short lived, and (III) fluorescently labeling the autophagy machinery or its cargo to specifically target those structures during focused ion beam (FIB) milling and tomogram acquisition.Using this approach, we captured the major membrane structures in bulk autophagy within their native context and at high resolution. Our detailed data analysis provides important insights into the biophysics of autophagosome biogenesis. While we focus here on yeast autophagy, our study highlights the potential of correlative cryo-ET in analyzing short-lived cellular structures and provides a general template for studying the formation of organelles. 相似文献
438.
439.
成骨细胞是骨修复重建的关键细胞,其增殖、分化、矿化的异常是骨质疏松症等骨代谢疾病的主要发病原因。线粒体在成骨细胞成骨功能中的调控作用不容忽视。近年研究发现,线粒体调控成骨细胞的能力,主要和线粒体氧化磷酸化、线粒体生物发生、线粒体动力学、线粒体自噬介导线粒体数量和功能的维持、为细胞提供能量及信号传导密切相关。本文综述了近年来线粒体调控成骨细胞功能的相关研究进展。 相似文献
440.