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951.
Wei Zhang Hongqi Feng Yanhui Gao Liyan Sun Jing Wang Yuanyuan Li Cheng Wang Lijun Zhao Xinxin Hu Huixin Sun Yudan Wei Dianjun Sun 《Biological trace element research》2013,151(2):269-276
Although studies have shown that arsenic exposure can induce apoptosis in a variety of cells, the exact molecular mechanism of chronic arsenicosis remains unclear. Based on our previous study on human serum, the present study was to determine whether pigment epithelium-derived factor (PEDF) plays a role in the damage induced by chronic arsenic exposure in a rat model and to explore the possible signaling pathway involved. Thirty male Wistar rats were randomly divided into three groups and the arsenite doses administered were 0, 10, and 50 mg/L, respectively. The experiment lasted for 6 months. Our results showed that level of arsenic increased significantly in serum, liver, brain, and kidney in arsenic-exposed groups. It was indicated that PEDF protein was widely distributed in the cytoplasm of various types of cells in liver, brain, and kidney. PEDF protein level was only changed when the arsenite dose reached 50 mg/L in liver and brain, whereas it was not changed in the kidney. In order to investigate the possible mechanism of PEDF-exerted damages upon arsenite exposure, apoptosis in liver and brain was assessed. The proportion of apoptotic cells gradually increased with increasing arsenic administration. The ratio of Bax/Bcl-2 in the high arsenic group (50 mg/L) was significantly higher than that in the control group. Therefore, we thought PEDF played a role in cell apoptosis of liver and brain which induced by sodium arsenite exposure, and the results also demonstrated that Bax and Bcl-2 might be two key targets in the action of PEDF. 相似文献
952.
Significant changes of copper homeostasis were triggered by lipopolysaccharides, which result in systemic inflammatory response and contribute to hepatic injury. Administration of lipopolysaccharides resulted in the increase of plasma “free” copper and total copper concentrations, whereas, the decrease of “free” copper and total copper contents in liver tissue. Copper-associated proteins were detected and showed a down-regulation of X-linked inhibitor of apoptosis protein, and up-regulation of copper metabolism domain containing 1 and copper transporter 1. The alteration of these proteins would lower the apoptotic threshold. Meanwhile, the increasing of circulation copper might cause oxidative injury through Fenton reaction and contribute to tissue injury. Our findings underscored the possibility that these changes in systemic copper homeostasis might provide a novel insight of the characteristic of the acute phase of inflammatory response and the underlying influence on tissue injury. 相似文献
953.
Jing Zhang Yang Zhou Lin Ma Shunquan Huang Ruijin Wang Rongrong Gao Youjun Wu Hongjun Shi Jun Zhang 《Biological trace element research》2013,152(2):267-274
Nickel is an important kind of metal and a necessary trace element in people’s production and livelihood; it is also a well-confirmed human carcinogen. In the past few years, researchers did a large number of studies about the molecular mechanisms of nickel carcinogenesis, and they focused on activation of proto-oncogenes and inactivation of anti-oncogenes caused by gene point mutation, gene deletion, gene amplification, DNA methylation, chromosome condensation, and so on that were induced by nickel. However, the researches on tumorigenic molecular mechanisms regulated by microRNAs (miRNAs) are rare. In this study, we established nickel-induced tumor by injecting Ni3S2 compounds to Wistar Rattus. By establishing a cDNA library of miRNA from rat muscle tumor tissue induced by Ni3S2, we found that the expression of miR-222 was significantly upregulated in tumor tissue compared with the normal tissue. As we expected, the expression levels of target genes of miR-222, CDKN1B and CDKN1C, were downregulated in the nickel-induced tumor. The same alteration of miR-222 and its target genes was also found in malignant 16HBE cells induced with Ni3S2 compounds. We conclude that miR-222 may promote cell proliferation infinitely during nickel-induced tumorigenesis in part by regulating the expression of its target genes CDKN1B and CDKN1C. Our study elucidated a novel molecular mechanism of nickel-induced tumorigenesis. 相似文献
954.
Xiaofei Liu Nan Zuo Huanan Guan Chunran Han Shi Wen Xu 《Biological trace element research》2013,154(2):202-209
Exposure to Manganese (Mn) is a common phenomenon due to its environmental pervasiveness. To investigate the Mn-induced toxicity on cerebral trace element levels and crucial nitric oxide parameters on brain of birds, 50-day-old male Hyline cocks were fed either a commercial diet or a Mn-supplemented diet containing 600, 900, 1,800 mg kg?1. After being treated with Mn for 30, 60, and 90 days, the following were determined: the changes in contents of copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), selenium (Se) in brain; inducible nitric oxide synthase-nitric oxide (iNOS-NO) system activity in brain; and histopathology and ultrastructure changes of cerebral cortex. The results showed that Mn was accumulated in brain and the content of Cu and Fe increased. However, the levels of Zn and Se decreased and the Ca content presented no obvious regularity. Exposure to Mn significantly elevated the content of NO and the expression of iNOS mRNA. Activity of total NO synthase (T NOS) and iNOS appeared with an increased tendency. These findings suggested that Mn exposure resulted in the imbalance of cerebral trace elements and influenced iNOS in the molecular level, which are possible underlying nervous system injury mechanisms induced by Mn exposure. 相似文献
955.
Zhaomin Li Hui Peng Li Qin Jing Qi Xiaobing Zuo Jing-Yuan Liu Jian-Ting Zhang 《The Journal of biological chemistry》2013,288(44):31447-31457
Many proteins exist and function as homodimers. Understanding the detailed mechanism driving the homodimerization is important and will impact future studies targeting the “undruggable” oncogenic protein dimers. In this study, we used 14-3-3σ as a model homodimeric protein and performed a systematic investigation of the potential roles of amino acid residues in the interface for homodimerization. Unlike other members of the conserved 14-3-3 protein family, 14-3-3σ prefers to form a homodimer with two subareas in the dimeric interface that has 180° symmetry. We found that both subareas of the dimeric interface are required to maintain full dimerization activity. Although the interfacial hydrophobic core residues Leu12 and Tyr84 play important roles in 14-3-3σ dimerization, the non-core residue Phe25 appears to be more important in controlling 14-3-3σ dimerization activity. Interestingly, a similar non-core residue (Val81) is less important than Phe25 in contributing to 14-3-3σ dimerization. Furthermore, dissociating dimeric 14-3-3σ into monomers by mutating the Leu12, Phe25, or Tyr84 dimerization residue individually diminished the function of 14-3-3σ in resisting drug-induced apoptosis and in arresting cells at G2/M phase in response to DNA-damaging treatment. Thus, dimerization appears to be required for the function of 14-3-3σ. 相似文献
956.
Tyler Schwend Zhigang Jin Kai Jiang Brian J. Mitchell Jianhang Jia Jing Yang 《The Journal of biological chemistry》2013,288(45):32809-32820
957.
Jing Jin Yuxiang Zheng William E. Boeglin Alan R. Brash 《Journal of lipid research》2013,54(3):754-761
Leukotriene (LT)A4 and closely related allylic epoxides are pivotal intermediates in lipoxygenase (LOX) pathways to bioactive lipid mediators that include the leukotrienes, lipoxins, eoxins, resolvins, and protectins. Although the structure and stereochemistry of the 5-LOX product LTA4 is established through comparison to synthetic standards, this is the exception, and none of these highly unstable epoxides has been analyzed in detail from enzymatic synthesis. Understanding of the mechanistic basis of the cis or trans epoxide configuration is also limited. To address these issues, we developed methods involving biphasic reaction conditions for the LOX-catalyzed synthesis of LTA epoxides in quantities sufficient for NMR analysis. As proof of concept, human 15-LOX-1 was shown to convert 15S-hydroperoxy-eicosatetraenoic acid (15S-HPETE) to the LTA analog 14S,15S-trans-epoxy-eicosa-5Z,8Z,10E,12E-tetraenoate, confirming the proposed structure of eoxin A4. Using this methodology we then showed that recombinant Arabidopsis AtLOX1, an arachidonate 5-LOX, converts 5S-HPETE to the trans epoxide LTA4 and converts 5R-HPETE to the cis epoxide 5-epi-LTA4, establishing substrate chirality as a determinant of the cis or trans epoxide configuration. The results are reconciled with a mechanism based on a dual role of the LOX nonheme iron in LTA epoxide biosynthesis, providing a rational basis for understanding the stereochemistry of LTA epoxide intermediates in LOX-catalyzed transformations. 相似文献
958.
Seongah Han Taro E. Akiyama Stephen F. Previs Kithsiri Herath Thomas P. Roddy Kristian K. Jensen Hong-Ping Guan Beth A. Murphy Lesley A. McNamara Xun Shen Walter Strapps Brian K. Hubbard Shirly Pinto Cai Li Jing Li 《Journal of lipid research》2013,54(10):2615-2622
Hepatic glucose overproduction is a major characteristic of type 2 diabetes. Because glucagon is a key regulator for glucose homeostasis, antagonizing the glucagon receptor (GCGR) is a possible therapeutic strategy for the treatment of diabetes mellitus. To study the effect of hepatic GCGR inhibition on the regulation of lipid metabolism, we generated siRNA-mediated GCGR knockdown (si-GCGR) in the db/db mouse. The hepatic knockdown of GCGR markedly reduced plasma glucose levels; however, total plasma cholesterol was increased. The detailed lipid analysis showed an increase in the LDL fraction, and no change in VLDL HDL fractions. Further studies showed that the increase in LDL was the result of over-expression of hepatic lipogenic genes and elevated de novo lipid synthesis. Inhibition of hepatic glucagon signaling via siRNA-mediated GCGR knockdown had an effect on both glucose and lipid metabolism in db/db mice. 相似文献
959.
Juan Ma Shulong Chen Maurice Moens Patrick De Clercq Xiuhua Li Richou Han 《Journal of invertebrate pathology》2013
In a series of bioassays, thirty-one isolates that were collected from diverse locations in northern China and the laboratory kept isolate Steinernema carpocapsae All, were compared in order to select superior isolates for biological control of Bradysia odoriphaga. Virulence of the isolates against B. odoriphaga was significantly different among nematode isolates. Tolerance of infective juveniles (IJs) to heat, cold, and desiccation differed significantly among and within species. Strains from S. carpocapsae, S. ceratophorum, S. longicaudum, Heterorhabditis indica, and H. bacteriophora were more heat tolerant than strains from S. feltiae, S. hebeiense, S. monticolum, and H. megidis. Heterorhabditis megidis, H. bacteriophora, and S. carpocapsae showed better cold tolerance than the other species. High desiccation tolerance was recorded for S. carpocapsae, S. hebeiense, and S. ceratophorum. The infectivity of IJ of these species against Galleria mellonella larvae was not significantly different between the treated and non-treated IJ after the nematodes had been exposed to 40 °C for 2 h, −5 °C for 8 h or 25% glycerin for 72 h. Nematode survival was significantly affected by exposure time and IJ concentration when exposed to 40 °C or −5 °C. All nematode isolates lost their infectivity against G. mellonella after exposure to −5 °C for 16 h, except for H. megidis LFS10, which had a low infectivity of 3.3%. A hierarchical classification analysis classified the isolates in four main clusters. The fourth cluster, composed of 13 isolates, grouped the isolates that scored well for most traits. 相似文献
960.
Alison M. Strack Ester Carballo-Jane Sheng-ping Wang Jiyan Xue Xiaoli Ping Lesley Ann McNamara Anil Thankappan Olga Price Michael Wolff T. J. Wu Douglas Kawka Michele Mariano Charlotte Burton Ching H. Chang Jing Chen John Menke Silvi Luell Emanuel I. Zycband Xinchun Tong Richard Raubertas Carl P. Sparrow Brian Hubbard John Woods Gary O'Neill M. Gerard Waters Ayesha Sitlani 《Journal of lipid research》2013,54(1):177-188
The use of nicotinic acid to treat dyslipidemia is limited by induction of a “flushing” response, mediated in part by the interaction of prostaglandin D2 (PGD2) with its G-protein coupled receptor, DP1 (Ptgdr). The impact of DP1 blockade (genetic or pharmacologic) was assessed in experimental murine models of atherosclerosis. In Ptgdr−/−ApoE−/− mice versus ApoE−/− mice, both fed a high-fat diet, aortic cholesterol content was modestly higher (1.3- to 1.5-fold, P < 0.05) in Ptgdr−/−ApoE−/− mice at 16 and 24 weeks of age, but not at 32 weeks. In multiple ApoE−/− mouse studies, a DP1-specific antagonist, L-655, generally had a neutral to beneficial effect on aortic lipids in the presence or absence of nicotinic acid treatment. In a separate study, a modest increase in some atherosclerotic measures was observed with L-655 treatment in Ldlr−/− mice fed a high-fat diet for 8 weeks; however, this effect was not sustained for 16 or 24 weeks. In the same study, treatment with nicotinic acid alone generally decreased plasma and/or aortic lipids, and addition of L-655 did not negate those beneficial effects. These studies demonstrate that inhibition of DP1, with or without nicotinic acid treatment, does not lead to consistent or sustained effects on plaque burden in mouse atherosclerotic models. 相似文献