全文获取类型
收费全文 | 472篇 |
免费 | 29篇 |
国内免费 | 3篇 |
专业分类
504篇 |
出版年
2022年 | 3篇 |
2021年 | 5篇 |
2020年 | 5篇 |
2019年 | 7篇 |
2018年 | 8篇 |
2017年 | 3篇 |
2016年 | 9篇 |
2015年 | 17篇 |
2014年 | 11篇 |
2013年 | 32篇 |
2012年 | 27篇 |
2011年 | 28篇 |
2010年 | 21篇 |
2009年 | 19篇 |
2008年 | 36篇 |
2007年 | 25篇 |
2006年 | 32篇 |
2005年 | 31篇 |
2004年 | 36篇 |
2003年 | 19篇 |
2002年 | 15篇 |
2001年 | 13篇 |
2000年 | 7篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 8篇 |
1994年 | 1篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 6篇 |
1982年 | 10篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 4篇 |
1972年 | 1篇 |
1966年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有504条查询结果,搜索用时 15 毫秒
11.
12.
Hiroto Ueba Masashi Shiomi Michael Brines Michael Yamin Tsutomu Kobayashi Junya Ako Shin-ichi Momomura Anthony Cerami Masanobu Kawakami 《Molecular medicine (Cambridge, Mass.)》2013,19(1):195-202
Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (≈70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-α and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-α expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-α production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease. 相似文献
13.
Yachiyo Sasaki Satoko Ohfuji Wakaba Fukushima Akihiro Tamori Masaru Enomoto Daiki Habu Shuji Iwai Sawako Uchida-Kobayashi Hideki Fujii Susumu Shiomi Norifumi Kawada Yoshio Hirota 《PloS one》2013,8(12)
Introduction
To date, there have been no prospective studies examining the effect of coffee consumption on serum alanine aminotransferase (ALT) level among individuals infected with the hepatitis C virus (HCV). We conducted a hospital-based cohort study among patients with chronic HCV infection to assess an association between baseline coffee consumption and subsequent ALT levels for 12 months.Materials and Methods
From 1 August 2005 to 31 July 2006, total 376 HCV-RNA positive patients were recruited. A baseline questionnaire elicited information on the frequency of coffee consumption and other caffeine-containing beverages. ALT level as a study outcome was followed through the patients’ medical records during 12 months. The association between baseline beverage consumption and subsequent ALT levels was evaluated separately among patients with baseline ALT levels within normal range (≤45 IU/L) and among those with higher ALT levels (>45 IU/L).Results
Among 229 patients with baseline ALT levels within normal range, 186 (81%) retained normal ALT levels at 12 months after recruitment. Daily drinkers of filtered coffee were three times more likely to preserve a normal ALT level than non-drinkers (OR=2.74; P=0.037). However, decaffeinated coffee drinkers had a somewhat inverse effect for sustained normal ALT levels, with marginal significance (OR=0.26; P=0.076). In addition, among 147 patients with higher baseline ALT levels, 39 patients (27%) had ALT reductions of ≥20 IU/L at 12 months after recruitment. Daily drinkers of filtered coffee had a significantly increased OR for ALT reduction (OR=3.79; P=0.034). However, in decaffeinated coffee drinkers, OR could not be calculated because no patients had ALT reduction.Conclusion
Among patients with chronic HCV infection, daily consumption of filtered coffee may have a beneficial effect on the stabilization of ALT levels. 相似文献14.
Yasushi Toge Yukihide Nishimura Jeffrey R. Basford Takako Nogawa Midori Yamanaka Takeshi Nakamura Munehito Yoshida Akira Nagano Fumihiro Tajima 《PloS one》2013,8(12)
Objective
To assess the separate effects of thumb and finger extension/flexion on median nerve position and cross-sectional area.Methods
Ultrasonography was used to assess median nerve transverse position and cross-sectional area within the carpal tunnel at rest and its movement during volitional flexion of the individual digits of the hand. Both wrists of 165 normal subjects (11 men, 4 women, mean age, 28.6, range, 22 to 38) were studied.Results
Thumb flexion resulted in transverse movement of the median nerve in radial direction (1.2±0.6 mm), whereas flexion of the fingers produced transverse movement in ulnar direction, which was most pronounced during flexion of the index and middle fingers (3.2±0.9 and 3.1±1.0 mm, respectively). Lesser but still statistically significant movements were noted with flexion of the ring finger (2.0±0.8 mm) and little finger (1.2±0.5 mm). Flexion of the thumb or individual fingers did not change median nerve cross-sectional area (8.5±1.1 mm2).Conclusions
Volitional flexion of the thumb and individual fingers, particularly the index and middle fingers, produced significant transverse movement of the median nerve within the carpal tunnel but did not alter the cross-sectional area of the nerve. The importance of these findings on the understanding of the pathogenesis of the carpal tunnel syndrome and its treatment remains to be investigated. 相似文献15.
Oral Candida Mannan Concentrations Correlate with Symptoms/Signs of Ill Health and the Immune Status
Hakoyama Yusuke Yamada Shin-ichi Nishimaki Fumihiro Hayashi Kiyonori Koizumi Tomonobu Kurita Hiroshi 《Mycopathologia》2020,185(4):629-637
Mycopathologia - A relationship has been proposed between increases in oral Candida concentrations and host immunity. Therefore, the present study was conducted to investigate the relationship... 相似文献
16.
Hiroko Bannai Fumihiro Niwa Shigeo Sakuragi Katsuhiko Mikoshiba 《Development, growth & differentiation》2020,62(6):398-406
The GABAergic synapses, a primary inhibitory synapse in the mammalian brain, is important for the normal development of brain circuits, and for the regulation of the excitation-inhibition balance critical for brain function from the developmental stage throughout life. However, the molecular mechanism underlying the formation, maintenance, and modulation of GABAergic synapses is less understood compared to that of excitatory synapses. Quantum dot-single particle tracking (QD-SPT), a super-resolution imaging technique that enables the analysis of membrane molecule dynamics at single-molecule resolution, is a powerful tool to analyze the behavior of proteins and lipids on the plasma membrane. In this review, we summarize the recent application of QD-SPT in understanding of GABAergic synaptic transmission. Here we introduce QD-SPT experiments that provide further insights into the molecular mechanism supporting GABAergic synapses. QD-SPT studies revealed that glutamate and Ca2+ signaling is involved in (a) the maintenance of GABAergic synapses, (b) GABAergic long-term depression, and GABAergic long-term potentiation, by specifically activating signaling pathways unique to each phenomenon. We also introduce a novel Ca2+ imaging technique to describe the diversity of Ca2+ signals that may activate the downstream signaling pathways that induce specific biological output. 相似文献
17.
Hema Balakrishna Bhat Takuma Kishimoto Mitsuhiro Abe Asami Makino Takehiko Inaba Motohide Murate Naoshi Dohmae Atsushi Kurahashi Kozo Nishibori Fumihiro Fujimori Peter Greimel Reiko Ishitsuka Toshihide Kobayashi 《Journal of lipid research》2013,54(10):2933-2943
A mixture of sphingomyelin (SM) and cholesterol (Chol) exhibits a characteristic lipid raft domain of the cell membranes that provides a platform to which various signal molecules as well as virus and bacterial proteins are recruited. Several proteins capable of specifically binding either SM or Chol have been reported. However, proteins that selectively bind to SM/Chol mixtures are less well characterized. In our screening for proteins specifically binding to SM/Chol liposomes, we identified a novel ortholog of Pleurotus ostreatus, pleurotolysin (Ply)A, from the extract of edible mushroom Pleurotus eryngii, named PlyA2. Enhanced green fluorescent protein (EGFP)-conjugated PlyA2 bound to SM/Chol but not to phosphatidylcholine/Chol liposomes. Cell surface labeling of PlyA2-EGFP was abolished after sphingomyelinase as well as methyl-β-cyclodextrin treatment, removing SM and Chol, respectively, indicating that PlyA2-EGFP specifically binds cell surface SM/Chol rafts. Tryptophan to alanine point mutation of PlyA2 revealed the importance of C-terminal tryptophan residues for SM/Chol binding. Our results indicate that PlyA2-EGFP is a novel protein probe to label SM/Chol lipid domains both in cell and model membranes. 相似文献
18.
Masaki Wakasugi Hiroaki Gouda Tomoyasu Hirose Akihiro Sugawara Tsuyoshi Yamamoto Kazuro Shiomi Toshiaki Sunazuka Satoshi Ōmura Shuichi Hirono 《Bioorganic & medicinal chemistry》2013,21(11):3214-3220
Human acidic mammalian chitinase (hAMCase) was recently shown to be involved in the development of asthma, suggesting a possible application for hAMCase inhibitors as novel therapeutic agents for asthma. We therefore initiated drug discovery research into hAMCase using a combination of in silico methodologies and a hAMCase assay system. We first selected 23 candidate hAMCase inhibitors from a database of four million compounds using a multistep screening system combining Tripos Topomer Search technology, a docking calculation and two-dimensional molecular similarity analysis. We then measured hAMCase inhibitory activity of the selected compounds and identified seven compounds with IC50 values ?100 μM. A model describing the binding modes of these hit compounds to hAMCase was constructed, and we discuss the structure–activity relationships of the compounds we identified, suggested by the model and the actual inhibitory activities of the compounds. 相似文献
19.
Norio Shiomi Jiro Yamada Masao Izawa 《Bioscience, biotechnology, and biochemistry》2013,77(11):2233-2244
Nine fructo-oligosaccharides, synthesized in vitro from sucrose by an enzyme preparation from asparagus roots, were isolated and their structures were elucidated to be 1F (1-β-fructofuranosyl)n sucrose [n = 1 (1-kestose), 2 (nystose) and 3], 6G (1-β-fructofuranosyl)n sucrose [n=1 (neokestose), 2 and 3] and 1F (1-β-fructofuranosyl)m-6G (1-β-fructofuranosyl)n sucrose [m=1, n=1; m=2, n =1; and m =1, n=2]. These saccharides are all known to occur naturally in asparagus roots, but 6G (1-β-fructofuranosyl)3 sucrose and 1F (1-β-fructofuranosyl)m-6G-(1-β-fructofuranosyl)n sucrose (m=1, n =1; and m=1, n=2) were the first saccharides enzymatically synthesized in vitro. Also three types of fructosyltransferases were presumed to be involved in the biosynthesis of these oligosaccharides in asparagus roots. 相似文献
20.
Takashi Utagawa Hirokazu Morisawa Shigeru Yamanaka Akihiro Yamazaki Fumihiro Yoshinaga Yoshio Hirose 《Bioscience, biotechnology, and biochemistry》2013,77(11):3239-3246
The properties of uridine Phosphorylase (UPase) and purine nucleoside Phosphorylase (PNPase) at high temperature were investigated. Both enzymes were found to be distributed in a wide range of bacteria and were partially purified from Enterobacter aerogenes AJ 11125 by heat treatment, ammonium sulfate fractionation and column chromatographies onDEAE-cellulose and Sephadex G-150. The UPase was purified 109-fold, and it showed an optimum pH of 8.5 and optimum temperature of 65°C, and activity toward uridine, 2′-deoxyuridine, thymidine and uracil arabinoside but not cytidine. The Km values of UPase for uridine were 0.7 mm at 40°C and 1.8 mm at 60°C. The PNPase was purified 83-fold, and it showed an optimum pH of 6.8 and optimum temperature of 60°C, and significant activity toward purine arabinosides as well as purine ribosides. The Km values of PNPase for inosine were 0.8 mm at 40°C and 2.2 mm at 60°C. 相似文献