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1.
Subcutaneous pretreatment of rats with neurokinin (NK) A or the fragment NKA(4-10) reduced the degree of gastric lesions induced by oral administration of 96% ethanol. The protective effect of NKA(4-10) was dose-dependent. Arg-NKB, the water soluble derivative of NKB, was less effective than NKA or NKA(4-10) while [Me-Phe7]NKB, substance P (SP) and SP-methyl-ester were inactive. The NKA(4-10) antilesion effect was reversed by pretreatment with N-ethyl-maleimide, suggesting a possible involvement of sulphydryls in its action. Among the nonmammalian tachykinins, kassinin significantly reduced ethanol-induced lesions while eledoisin and physalaemin at equivalent molar doses were inactive. These results provide, for the first time, evidence that tachykinins and their derivatives exert gastroprotective activity toward ethanol-induced haemorrhagic lesions. Assuming a receptor-mediated mechanism, NK-2 sites could be involved. 相似文献
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Nicola Maggiano Franco Citterio Antonella Evangelista Ubaldo Pozzetto Marco Castagneto Arnaldo Capelli 《The Histochemical journal》1994,26(7):553-562
Summary The targets of preformed natural antibodies need to be identified whenever the use of pig organs is considered for human transplantation. In this study we used extracorporeal perfusion of pig organs with human blood, immunocytological techniques and immuno-electron microscopy to identify the targets and the nature of human preformed natural antibodies against pig antigens. The antibodies were found to be mainly of the IgG and IgM type and directed not only against endothelial cells, but also against mesenchymal and epithelial structures. To reproduce an in vivo situation, a Bio-pump was used to xenoperfuse pig kidneys and livers with human fresh oxygenated blood at 37°C, drawn from polycythaemic patients. Biopsies showed a deposition of human IgG and IgM on tubuli and glomeruli of pig kidneys and on endothelial cells of pig livers. Preperfusion of pig liver with human blood for 45 minutes before perfusion of kidneys significantly reduced the deposition of the natural antibodies. 相似文献
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Valter Bergant Shintaro Yamada Vincent Grass Yuta Tsukamoto Teresa Lavacca Karsten Krey MariaTeresa Mühlhofer Sabine Wittmann Armin Ensser Alexandra Herrmann Anja vom Hemdt Yuriko Tomita Shutoku Matsuyama Takatsugu Hirokawa Yiqi Huang Antonio Piras Constanze A Jakwerth Madlen Oelsner Susanne Thieme Alexander Graf Stefan Krebs Helmut Blum Beate M Kümmerer Alexey Stukalov Carsten B SchmidtWeber Manabu Igarashi Thomas Gramberg Andreas Pichlmair Hiroki Kato 《The EMBO journal》2022,41(17)
The SARS‐CoV‐2 infection cycle is a multistage process that relies on functional interactions between the host and the pathogen. Here, we repurposed antiviral drugs against both viral and host enzymes to pharmaceutically block methylation of the viral RNA 2''‐O‐ribose cap needed for viral immune escape. We find that the host cap 2''‐O‐ribose methyltransferase MTr1 can compensate for loss of viral NSP16 methyltransferase in facilitating virus replication. Concomitant inhibition of MTr1 and NSP16 efficiently suppresses SARS‐CoV‐2 replication. Using in silico target‐based drug screening, we identify a bispecific MTr1/NSP16 inhibitor with anti‐SARS‐CoV‐2 activity in vitro and in vivo but with unfavorable side effects. We further show antiviral activity of inhibitors that target independent stages of the host SAM cycle providing the methyltransferase co‐substrate. In particular, the adenosylhomocysteinase (AHCY) inhibitor DZNep is antiviral in in vitro, in ex vivo, and in a mouse infection model and synergizes with existing COVID‐19 treatments. Moreover, DZNep exhibits a strong immunomodulatory effect curbing infection‐induced hyperinflammation and reduces lung fibrosis markers ex vivo. Thus, multispecific and metabolic MTase inhibitors constitute yet unexplored treatment options against COVID‐19. 相似文献
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Cavite Harry Jay M. Mactal Ariel G. Evangelista Editha V. Cruz Jayvee A. 《Journal of Plant Growth Regulation》2021,40(2):494-508
Journal of Plant Growth Regulation - This study evaluated the effects of plant growth-promoting rhizobacteria (PGPR) isolates in enhancing upland rice growth and yield. Bacteria were isolated,... 相似文献
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Alice Toso Simona Schifano Charlotte Oxborough Krista McGrath Luke Spindler Anabela Castro Lucy Evangelista Vanessa Filipe Maria José Gonçalves Antonio Marques Inês Mendes da Silva Raquel Santos Maria João Valente Iona McCleery Michelle Alexander 《American journal of physical anthropology》2021,176(2):208-222
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The development of atherosclerosis is caused by the accumulation of lipid, inflammatory cytokine production, and the large amount of inflammatory cells in the arterial wall. It is now established that the presence of oxidized low-density lipoproteins (ox-LDL) has an important role in the pathogenesis of the disease. There are many scavenger receptors for ox-LDL, among which LOX-1 seems to be important for the induction of endothelial dysfunction and the other subsequent events that lead to the formation of atheromatous plaque. Our findings indicate the presence of a regulatory role induced by the presence of ox-LDL on LOX-1 through the amplification of IL-6 synthesis. This mechanism contributes to the upregulation of the ORL-1 gene expression in presence of risk factors. Many authors have shown the possibility to use LOX-1 as a good marker for the diagnosis and prognosis of coronary artery disease because it is easy to measure and more sensitive than other markers commonly used in the routine of laboratory medicine. 相似文献
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Lucas Cunha Dias de Rezende Fernando Fumagalli Marraiana Schiavon Bortolin Marianne Garcia de Oliveira Murilo Helder de Paula Valter Ferreira de Andrade-Neto Flavio da Silva Emery 《Bioorganic & medicinal chemistry letters》2013,23(16):4583-4586
1,4-Naphthoquinone derivatives are known to have relevant activities against several parasites. Among the treatment options for malaria, atovaquone, a 1,4-naphthoquinone derivative, is widely applied in the treatment and prophylaxis of such disease. Based on the structure simplification of atovaquone, we designed and synthesized four novel naphthoquinoidal derivatives. The compounds were obtained by the underexplored epoxide-opening reaction of 1,4-naphthoquinone using aniline derivatives as nucleophiles. The antiplasmodial activity of the synthesized compounds was performed in vivo using Peter’s 4 days suppression test. Significant parasitemia reduction and increased survival were observed for some of the compounds. 相似文献