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991.
Enzyme Kinetics of an Alternative Splicing Isoform of Mitochondrial 8‐Oxoguanine DNA Glycosylase,OGG1‐1b,and Compared with the Nuclear OGG1‐1a 下载免费PDF全文
Akira Ogawa Takashi Watanabe Sayaka Shoji Chie Furihata 《Journal of biochemical and molecular toxicology》2015,29(2):49-56
Eight alternatively spliced isoforms of human 8‐oxoguanine DNA glycosylase (OGG1) (OGG1‐1a to ‐1c and ‐2a to ‐2e) are registered in the National Center for Biotechnology Information. OGG1(s) in mitochondria have not yet been fully characterized biochemically. In this study, we purified mitochondrial recombinant OGG1‐1b protein and compared its activity with nuclear OGG1‐1a protein. The reaction rate constant (kg) of the 7,8‐dihydro‐8‐oxoguanine (8‐oxoG) glycosylase activity of OGG1‐1b was 8‐oxoG:C >> 8‐oxoG:T >> 8‐oxoG:G > 8‐oxoG:A (7.96, 0.805, 0.070, and 0.015 min?1, respectively) and that of the N‐glycosylase/DNA lyase activity (kgl) of OGG1‐1b was 8‐oxoG:C > 8‐oxoG:T ?8‐oxoG:G >> 8‐oxoG:A (0.286, 0.079, 0.040, and negligible min?1, respectively). These reaction rate constants were similar to those of OGG1‐1a except for kgl against 8‐oxoG:A. APEX nuclease 1 was required to promote DNA strand breakage by OGG1‐1b. These results suggest that OGG1‐1b is associated with 8‐oxoG cleavage in human mitochondria and that the mechanism of this repair is similar to that of nuclear OGG1‐1a. 相似文献
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Shinobu Kitazume Akiomi Yoshihisa Takayoshi Yamaki Masayoshi Oikawa Yuriko Tachida Kazuko Ogawa Rie Imamaki Yoshiaki Hagiwara Noriaki Kinoshita Yasuchika Takeishi Katsutoshi Furukawa Naoki Tomita Hiroyuki Arai Nobuhisa Iwata Takaomi Saido Naomasa Yamamoto Naoyuki Taniguchi 《The Journal of biological chemistry》2012,287(48):40817-40825
Most Alzheimer disease (AD) patients show deposition of amyloid β (Aβ) peptide in blood vessels as well as the brain parenchyma. We previously found that vascular endothelial cells express amyloid β precursor protein (APP) 770, a different APP isoform from neuronal APP695, and produce Aβ. Since the soluble APP cleavage product, sAPP, is considered to be a possible marker for AD diagnosis, sAPP has been widely measured as a mixture of these variants. We hypothesized that measurement of the endothelial APP770 cleavage product in patients separately from that of neuronal APP695 would enable discrimination between endothelial and neurological dysfunctions. Using our newly developed ELISA system for sAPP770, we observed that inflammatory cytokines significantly enhanced sAPP770 secretion by endothelial cells. Furthermore, we unexpectedly found that sAPP770 was rapidly released from activated platelets. We also found that cerebrospinal fluid mainly contained sAPP695, while serum mostly contained sAPP770. Finally, to test our hypothesis that sAPP770 could be an indicator for endothelial dysfunction, we applied our APP770 ELISA to patients with acute coronary syndrome (ACS), in which endothelial injury and platelet activation lead to fibrous plaque disruption and thrombus formation. Development of a biomarker is essential to facilitate ACS diagnosis in clinical practice. The results revealed that ACS patients had significantly higher plasma sAPP770 levels. Furthermore, in myocardial infarction model rats, an increase in plasma sAPP preceded the release of cardiac enzymes, currently used markers for acute myocardial infarction. These findings raise the possibility that sAPP770 can be a useful biomarker for ACS. 相似文献
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Iwabuchi K Nakayama H Masuda H Kina K Ogawa H Takamori K 《BioFactors (Oxford, England)》2012,38(4):275-283
Over the last 30 years, many studies have indicated that glycosphingolipids (GSLs) expressed on the cell surface may act as binding sites for microorganisms. Based on their physicochemical characteristics, GSLs form membrane microdomains with cholesterol, sphingomyelin, glycosylphosphatidylinositol (GPI)-anchored proteins, and various signaling molecules, and GSL-enriched domains have been shown to be involved in these defense responses. Among the GSLs, lactosylceramide (LacCer, CDw17) can bind to various microorganisms. LacCer is expressed at high levels on the plasma membrane of human neutrophils, and forms membrane microdomains associated with the Src family tyrosine kinase Lyn. LacCer-enriched membrane microdomains mediate superoxide generation, chemotaxis, and non-opsonic phagocytosis. Therefore, LacCer-enriched membrane microdomains are thought to function as pattern recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) expressed on microorganisms. In contrast, several pathogens have developed infection mechanisms using membrane microdomains. In addition, some pathogens have the ability to avoid degradation by escaping from the vacuolar compartment or preventing phagosome maturation, utilizing membrane microdomains, such as LacCer-enriched domains, of host cells. The detailed molecular mechanisms of these membrane microdomain-associated host-pathogen interactions remain to be elucidated. 相似文献
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Ogawa A 《Bioorganic & medicinal chemistry letters》2012,22(4):1639-1642
A strategy for rationally constructing a novel type of eukaryotic OFF-riboswitch, which ligand-dependently turns off translation mediated by an internal ribosome entry site (IRES), has been established. The theophylline-dependent IRES-based OFF-riboswitch obtained through the proposed strategy functioned well in wheat germ extract, independently from the downstream gene, indicating that it can regulate any gene. Despite the fact that it has one theophylline aptamer, its switching efficiency was as high as that of a previously reported theophylline-dependent OFF-riboswitch that was constructed by inserting three continuous theophylline aptamers into a 5' untranslated region in mRNA to downregulate the normal 5'-terminus-mediated translation. In addition, because the riboswitch part that was optimized in the theophylline-dependent IRES-based OFF-riboswitch, except for the aptamer domain, can be used as-is for other aptamer-ligand pairs, an arbitrary ligand-dependent IRES-based OFF-riboswitch is easy to construct with the corresponding well-minimized aptamer. 相似文献
998.
Asakawa C Ogawa M Fujinaga M Kumata K Xie L Yamasaki T Yui J Fukumura T Zhang MR 《Bioorganic & medicinal chemistry letters》2012,22(11):3594-3597
N-(2-{3-[3,5-Bis(trifluoromethyl)]phenylureido}ethyl)glycyrrhetinamide (2), an ureido-substituted derivative of glycyrrhetinic acid (1), has been reported to display potent inhibitory activity for proteasome and kinase, which are overexpressed in tumors. In this study, we labeled this unsymmetrical urea 2 using [(11)C]phosgene ([(11)C]COCl(2)) as a labeling agent with the expectation that [(11)C]2 could become a positron emission tomography ligand for the imaging of proteasome and kinase in tumors. The strategy for the radiosynthesis of [(11)C]2 was to react hydrochloride of 3,5-bis(trifluoromethyl)aniline (4·HCl) with [(11)C]COCl(2) to possibly give isocyanate [(11)C]6, followed by the reaction of [(11)C]6 with N-(2-aminoethyl)glycyrrhetinamide (3). 相似文献
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Yutaka Mori Yasuyuki Ogawa Akiyoshi Mochizuki Yuji Nakamura Chie Sugita Shojiro Miyazaki Kazuhiko Tamaki Yumi Matsui Mizuki Takahashi Takahiro Nagayama Yoko Nagai Shin-ichi Inoue Takahide Nishi 《Bioorganic & medicinal chemistry letters》2012,22(24):7677-7682
Utilizing X-ray crystal structure analysis, (3S,5R)-5-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]piperidine-3-carboxamides were designed and identified as renin inhibitors. The most potent compound 15 demonstrated favorable pharmacokinetic and pharmacodynamic profiles in rat. 相似文献
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