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31.
Jinjin Shao Zhifei Xu Xueming Peng Min Chen Yuanrun Zhu Li Xu Hong Zhu Bo Yang Peihua Luo Qiaojun He 《PloS one》2016,11(1)
Chemotherapy is the only choice for most of the advanced hepatocellular carcinoma (HCC) patients, while few agents were available, making it an urgent need to develop new chemotherapy strategies. A phase II clinical trial suggested that the efficacy of irinotecan in HCC was limited due to dose-dependent toxicities. Here, we found that gefitinib exhibited synergistic activity in combination with SN-38, an active metabolite of irinotecan, in HCC cell lines. And the enhanced apoptosis induced by gefitinib plus SN-38 was a result from caspase pathway activation. Mechanistically, gefitinib dramatically promoted the ubiquitin–proteasome-dependent degradation of Rad51 protein, suppressed the DNA repair, gave rise to more DNA damages, and ultimately resulted in the synergism of these two agents. In addition, the increased antitumor efficacy of gefitinib combined with irinotecan was further validated in a HepG2 xenograft mice model. Taken together, our data demonstrated for the first time that the combination of irinotecan and gefitinib showed potential benefit in HCC, which suggests that Rad51 is a promising target and provides a rationale for clinical trials investigating the efficacy of the combination of topoisomerase I inhibitors and gefitinib in HCC. 相似文献
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Chong Gang-Gang Huang Xiao-Jun Di Jun-Hua Xu Dao-Zhu He Yu-Cai Pei Ya-Nan Tang Ya-Jie Ma Cui-Luan 《Bioprocess and biosystems engineering》2018,41(4):501-510
Bioprocess and Biosystems Engineering - Based on the Prussian blue spectrophotometric method, one high-throughput screening strategy for screening lignin-degrading microorganisms was built on... 相似文献
34.
Xinyao Zhu Srdjan Cirovic Aliah Shaheen Wei Xu 《Biomechanics and modeling in mechanobiology》2018,17(3):665-674
In this study, atomic force microscopy (AFM) is used to investigate the alterations of the poroelastic properties of hepatocellular carcinoma (SMMC-7721) cells treated with fullerenol. The SMMC-7721 cells were subject to AFM-based creep tests, and a corresponding poroelastic indentation model was used to determine the poroelastic parameters by curve fitting. Comparative analyses indicated that the both permeability and diffusion of fullerenol-treated cells increased significantly while their elastic modulus decreased by a small amount. From the change in the trend of the determined parameter, we verified the corresponding alternations of cytoskeleton (mainly filaments actin), which was reported by the previous study using confocal imaging method. Our investigation on SMMC-7721 cell reveals that the poroelastic properties could provide a better understanding how the cancer cells are affected by fullerenol or potentially other drugs which could find possible applications in drug efficacy test, cancer diagnosis and secure therapies. 相似文献
35.
Yilin Zhu 《Biomechanics and modeling in mechanobiology》2018,17(6):1875-1883
In the present work, a constitutive model for articular cartilage is proposed in finite elasto-viscoplasticity. For simplification, articular cartilage is supposed to be a typical composite composed of a soft basis and a fiber assembly. The stress tensor and free energy function are hence accordingly divided into two components. The high nonlinear stress-strain response is assumed to be mainly related to the fiber assembly and described by an exponential-type hypoelastic relation. Ratcheting is considered according to the viscoplasticity, the evolution rule of which is deduced from the dissipative inequality by the co-directionality hypotheses. Then, the capability of the proposed model is validated by comparing its predictions with related experimental observations. Results show that the ratcheting behavior and stress-strain hysteresis loops are reasonably captured by the proposed model. 相似文献
36.
Glycogen debranching enzyme: purification, antibody characterization, and immunoblot analyses of type III glycogen storage disease. 总被引:2,自引:1,他引:1 下载免费PDF全文
Type III glycogen storage disease is caused by a deficiency of glycogen debranching-enzyme activity. Many patients with this disease have both liver and muscle involvement, whereas others have only liver involvement without clinical or laboratory evidence of myopathy. To improve our understanding of the molecular basis of the disease, debranching enzyme was purified 238-fold from porcine skeletal muscle. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis the purified enzyme gave a single band with a relative molecular weight of 160,000 that migrated to the same position as purified rabbit-muscle debranching enzyme. Antiserum against porcine debranching enzyme was prepared in rabbit. The antiserum reacted against porcine debranching enzyme with a single precipitin line and demonstrated a reaction having complete identity to those of both the enzyme present in crude muscle and the enzyme present in liver extracts. Incubation of antiserum with purified porcine debranching enzyme inhibited almost all enzyme activity, whereas such treatment with preimmune serum had little effect. The antiserum also inhibited debranching-enzyme activity in crude liver extracts from both pigs and humans to the same extent as was observed in muscle. Immunoblot analysis probed with anti-porcine-muscle debranching-enzyme antiserum showed that the antiserum can detect debranching enzyme in both human muscle and human liver. The bands detected in human samples by the antiserum were the same size as the one detected in porcine muscle. Five patients with Type III and six patients with other types of glycogen storage disease were subjected to immunoblot analysis. Although anti-porcine antiserum detected specific bands in all liver and muscle samples from patients with other types of glycogen storage disease (Types I, II, and IX), the antiserum detected no cross-reactive material in any of the liver or muscle samples from patients with Type III glycogen storage disease. These data indicate (1) immunochemical similarity of debranching enzyme in liver and muscle and (2) that deficiency of debranching-enzyme activity in Type III glycogen storage disease is due to absence of debrancher protein in the patients that we studied. 相似文献
37.
Yun Guo Yuejun He Pan Wu Bangli Wu Yan Lin Minhong He Xu Han Tingting Xia Kaiping Shen Liling Kang Qiyu Tan Wenda Ren Yan Sun Qing Li 《Journal of Plant Ecology》2022,15(2):399
AM 真菌和枯落物互作下两种喀斯特植物种间竞争较种内竞争更能促进植物养分利用
枯落物是植物养分获取和土壤养分转化的关键载体。丛枝菌根(Arbuscular mycorrhizae, AM)对植物养分摄取的影响已被广泛认知。然而,在养分亏缺的喀斯特生境中,不同竞争方式的植物如何通过AM真菌和枯落物利用养分尚不清楚。本研究对两种喀斯特适生植物构树(Broussonetia papyrifera)和云贵鹅耳枥(Carpinus pubescens)进行种内竞争和种 间竞争种植处理,并通过幼套球 囊霉(Glomus etunicatum)接种或不接种处理,以及土壤中添加或不添加两物种叶片混合枯落物处理,测定了植物生物量以及氮、磷、钾浓度等指标,研究植物的生长和养分利用。研究结果表明,AM真菌对两种植物养分摄取影响不同,AM真菌显著提高了种内和种间竞争下构树的养分摄取量,但降低了云贵鹅耳枥的养分摄取量。种间竞争下接种AM真菌,枯落物添加促进了云贵鹅耳枥对氮的摄取,抑制了构树对氮的摄取。接种AM真菌和添加枯落物条件下,种间竞争的构树对氮、磷和钾的摄取量及云贵鹅耳枥对氮的摄取量均高于种内竞争;种间竞争下两物种养分竞争力呈现明显差异,即构树对磷和钾养分竞争力显著提高,对氮则不显著;云贵鹅耳枥仅对钾的养分竞争力显著降低,对氮和磷则无显著影响。这些结果说明,在AM真菌与枯落物相互作用下,两种喀斯特植物种间竞争较种内竞争更能促进植物养分利用。 相似文献
38.
Ping Yuan Xiaoyu Qi Anping Song Mingyue Ma Xinbei Zhang Chunfeng Lu Mianli Bian Naqi Lian Jianling He Shuguo Zheng Huanhuan Jin 《Journal of cellular and molecular medicine》2021,25(15):7354-7366
Although recent evidence has shown that hepatocyte senescence plays a crucial role in the pathogenesis and development of non-alcoholic fatty liver disease (NAFLD), the mechanism is still not clear. The purpose of this study was to investigate the signal transduction pathways involved in the senescence of hepatocyte, in order to provide a potential strategy for blocking the process of NAFLD. The results confirmed that hepatocyte senescence occurred in HFD-fed Golden hamsters and PA-treated LO2 cells as manifested by increased levels of senescence marker SA-β-gal, p16 and p21, heterochromatin marker H3K9me3, DNA damage marker γ-H2AX and decreased activity of telomerase. Further studies demonstrated that iron overload could promote the senescence of hepatocyte, whereas the overexpression of Yes-associated protein (YAP) could blunt iron overload and alleviate the senescence of hepatocyte. Of importance, depression of lncRNA MAYA (MAYA) reduced iron overload and cellular senescence via promotion of YAP in PA-treated hepatocytes. These effects were further supported by in vivo experiments. In conclusion, these data suggested that inhibition of MAYA could up-regulate YAP, which might repress hepatocyte senescence through modulating iron overload. In addition, these findings provided a promising option for heading off the development of NAFLD by abrogating hepatocyte senescence. 相似文献
39.