全文获取类型
收费全文 | 1117篇 |
免费 | 55篇 |
国内免费 | 3篇 |
专业分类
1175篇 |
出版年
2022年 | 10篇 |
2021年 | 16篇 |
2020年 | 5篇 |
2019年 | 15篇 |
2018年 | 28篇 |
2017年 | 18篇 |
2016年 | 19篇 |
2015年 | 39篇 |
2014年 | 35篇 |
2013年 | 84篇 |
2012年 | 57篇 |
2011年 | 60篇 |
2010年 | 36篇 |
2009年 | 34篇 |
2008年 | 80篇 |
2007年 | 65篇 |
2006年 | 78篇 |
2005年 | 62篇 |
2004年 | 52篇 |
2003年 | 65篇 |
2002年 | 61篇 |
2001年 | 15篇 |
2000年 | 12篇 |
1999年 | 19篇 |
1998年 | 13篇 |
1997年 | 9篇 |
1996年 | 4篇 |
1995年 | 14篇 |
1994年 | 9篇 |
1993年 | 10篇 |
1992年 | 14篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 4篇 |
1988年 | 8篇 |
1987年 | 9篇 |
1986年 | 7篇 |
1985年 | 9篇 |
1984年 | 7篇 |
1983年 | 9篇 |
1982年 | 15篇 |
1981年 | 8篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1975年 | 7篇 |
1973年 | 2篇 |
1969年 | 3篇 |
排序方式: 共有1175条查询结果,搜索用时 15 毫秒
21.
Yukio Kitade Masaharu Wakana Shin-ichi Terai Takayuki Tsuboi Masayuki Nakanishi Chizuko Yatome 《Nucleosides, nucleotides & nucleic acids》2013,32(12):2323-2333
Abstract 2-Bromoadenosine-substituted analogues of 2–5A, p5′A2′p-5′A2′p5′(br2A), p5′(br2A)2′p5′A2′p5′A, and p5′(br2A)2′p5′(br2A)2′p-S′(br2A), were prepared via a modification of a lead ion-catalyzed ligation reaction and were subsequently converted into the corresponding 5′-triphosphates. Both binding and activation of human recombinant RNase L by various 2-bromoadenosine-substituted 2–5A analogues were examined. Among the 2-bromoadenosine-substituted 2–5A analogues, the analogue with 2-bromoadenosine residing in the 2′-terminal position, p5′A2′p5′A2′p-5′(br2A), showed the strongest binding affinity and was as effective as 2–5A itself as an activator of RNase L. The CD spectrum of p5′A2′p-5′A2′p5′(br2A) was superimposable on that of p5′A2′p5′A2′p5′A, indicative of an anti orientation about the base-glycoside bonds as in naturally occurring 2–5A. 相似文献
22.
Kiyoshi Migita Toru Arai Naoki Ishizuka Yuka Jiuchi Yasuharu Sasaki Yasumori Izumi Tetsuyuki Kiyokawa Eiichi Suematsu Tomoya Miyamura Hiroshi Tsutani Yojiro Kawabe Ryutaro Matsumura Shunsuke Mori Shiro Ohshima Shigeru Yoshizawa Kenji Kawakami Yasuo Suenaga Hideo Nishimura Toyohiko Sugimoto Hiroaki Iwase Hideyuki Sawada Haruhiro Yamashita Shigeyuki Kuratsu Fumitaka Ogushi Masaharu Kawabata Toshihiro Matsui Hiroshi Furukawa Seiji Bito Shigeto Tohma 《PloS one》2013,8(11)
Background/Aims
The Japanese National Hospital Organization evidence-based medicine (EBM) Study group for Adverse effects of Corticosteroid therapy (J-NHOSAC) is a Japanese hospital-based cohort study investigating the safety of the initial use of glucocorticoids (GCs) in patients with newly diagnosed autoimmune diseases. Using the J-NHOSAC registry, the purpose of this observational study is to analyse the rates, characteristics and associated risk factors of intracellular infections in patients with newly diagnosed autoimmune diseases who were initially treated with GCs.Methodology/Principal Findings
A total 604 patients with newly diagnosed autoimmune diseases treated with GCs were enrolled in this registry between April 2007 and March 2009. Cox proportional-hazards regression was used to determine independent risk factors for serious intracellular infections with covariates including sex, age, co-morbidity, laboratory data, use of immunosuppressants and dose of GCs. Survival was analysed according to the Kaplan-Meier method and was assessed by the log-rank test. There were 127 serious infections, including 43 intracellular infections, during 1105.8 patient-years of follow-up. The 43 serious intracellular infections resulted in 8 deaths. After adjustment for covariates, diabetes (Odds ratio [OR]: 2.5, 95% confidence interval [95% CI] 1.1–5.9), lymphocytopenia (≦1000/μl, OR: 2.5, 95% CI 1.2–5.2) and use of high-dose (≧30 mg/day) GCs (OR: 2.4, 95% CI 1.1–5.3) increased the risk of intracellular infections. Survival curves showed lower intracellular infection-free survival rate in patients with diabetes, lymphocytopaenia and high-dose GCs treatments.Conclusions/Significance
Patients with newly diagnosed autoimmune diseases were at high risk of developing intracellular infection during initial treatment with GCs. Our findings provide background data on the risk of intracellular infections of patients with autoimmune diseases. Clinicians showed remain vigilant for intracellular infections in patients with autoimmune diseases who are treated with GCs. 相似文献23.
24.
Fumiaki Nakayama Sachiko Umeda Tomomi Ichimiya Shin Kamiyama Masaharu Hazawa Takeshi Yasuda Shoko Nishihara Takashi Imai 《FEBS letters》2013,587(2):231-237
This study focuses on clarifying the contribution of sulfation to radiation-induced apoptosis in human Burkitt’s lymphoma cell lines, using 3′-phosphoadenosine 5′-phosphosulfate transporters (PAPSTs). Overexpression of PAPST1 or PAPST2 reduced radiation-induced apoptosis in Namalwa cells, whereas the repression of PAPST1 expression enhanced apoptosis. Inhibition of PAPST slightly decreased keratan sulfate (KS) expression, so that depletion of KS significantly increased radiation-induced apoptosis. In addition, the repression of all three N-acetylglucosamine-6-O-sulfotransferases (CHST2, CHST6, and CHST7) increased apoptosis. In contrast, PAPST1 expression promoted the phosphorylation of p38 MAPK and Akt in irradiated Namalwa cells. These findings suggest that 6-O-sulfation of GlcNAc residues in KS reduces radiation-induced apoptosis of human Burkitt’s lymphoma cells. 相似文献
25.
Salinization of crop fields is a pressing matter for sustainable agriculture under desertification and is largely attributed to root absorptive functions of the major crops such as maize. The rates of water and ion absorption of intact root system of maize plants were measured under the salinized condition, and the salt absorptive function of maize roots was analyzed by applying different two kinetic models of root ion absorption (i.e. the concentration dependent model and the transpiration integrated model). The absorption rates for salinization ions (Na+, Cl?, Ca2+ and Mg2+) were found to depend on ion mass flow through roots driven by the transpiration, and therefore the transpiration integrated model represented more accurately rates of root ion absorption. The root absorption of salinization ions was characterized quantitatively by two model parameters of Q′max and K′M involved in the transpiration integrated model, which are considered to relate to the potential absorbing power and the ion affinity of transport proteins on root cell membranes, respectively. 相似文献
26.
Taku Watanabe Ichizo Tsujino Satoshi Konno Yoichi M. Ito Chisa Takashina Takahiro Sato Akira Isada Hiroshi Ohira Yoshinori Ohtsuka Yuma Fukutomi Hiroyuki Nakamura Yukio Kawagishi Chiharu Okada Nobuyuki Hizawa Masami Taniguchi Akira Akasawa Masaharu Nishimura 《PloS one》2016,11(3)
Objective
A positive association between the number of cigarettes smoked per day and obesity has been reported, whereas how other smoking-related indices, such as pack-years and duration of smoking, are related with obesity has been less investigated. We analyzed the age-adjusted cross-sectional association between smoking and obesity in a general Japanese population.Methods
We used data from a nationwide epidemiological study of Japanese adults (N = 23,106). We compared the prevalence of obesity (defined as body mass index ≥ 25kg/m2) among groups classified by smoking behavior, pack-years, number of cigarettes per day, duration of smoking, and duration and time of smoking cessation.Results
In men, current smokers had a lower odds ratio (OR) for obesity of 0.80 (95% confidence interval (CI): 0.72–0.88) compared to non-smokers, whereas past smokers had a higher OR of 1.23 (95% CI: 1.09–1.37) compared to current smokers. In women, there were no differences in obesity between the three groups classified by smoking behavior. However, in both sexes, the prevalence of obesity tended to increase with pack-years and the number of cigarettes per day, but not with duration of smoking in current and past smokers. Further, in male smokers, the risks for obesity were markedly higher in short-term heavy smokers compared with long-term light smokers, even with the same number of pack-years. Regarding the impact of smoking cessation, female past smokers who quit smoking at an age > 55-years had an elevated OR of 1.60 (95% CI:1.05–2.38) for obesity.Conclusions
In a general Japanese population, obesity is progressively associated with pack-years and number of cigarettes per day, but not with the duration of smoking. When investigating the association between obesity and cigarette smoking, the daily smoking burden and the duration of smoking require to be independently considered. 相似文献27.
Naohiro Yoshida Jin Endo Kenichiro Kinouchi Hiroki Kitakata Hidenori Moriyama Masaharu Kataoka Tsunehisa Yamamoto Kohsuke Shirakawa Satoshi Morimoto Akira Nishiyama Akihiro Hashiguchi Itsuro Higuchi Keiichi Fukuda Atsuhiro Ichihara Motoaki Sano 《Aging cell》2019,18(5)
To extend life expectancy and ensure healthy aging, it is crucial to prevent and minimize age‐induced skeletal muscle atrophy, also known as sarcopenia. However, the disease's molecular mechanism remains unclear. The age‐related Wnt/β‐catenin signaling pathway has been recently shown to be activated by the (pro)renin receptor ((P)RR). We report here that (P)RR expression was increased in the atrophied skeletal muscles of aged mice and humans. Therefore, we developed a gain‐of‐function model of age‐related sarcopenia via transgenic expression of (P)RR under control of the CAG promoter. Consistent with our hypothesis, (P)RR‐Tg mice died early and exhibited muscle atrophy with histological features of sarcopenia. Moreover, Wnt/β‐catenin signaling was activated and the regenerative capacity of muscle progenitor cells after cardiotoxin injury was impaired due to cell fusion failure in (P)RR‐Tg mice. In vitro forced expression of (P)RR protein in C2C12 myoblast cells suppressed myotube formation by activating Wnt/β‐catenin signaling. Administration of Dickkopf‐related protein 1, an inhibitor of Wnt/β‐catenin signaling, and anti‐(P)RR neutralizing antibody, which inhibits binding of (P)RR to the Wnt receptor, significantly improved sarcopenia in (P)RR‐Tg mice. Furthermore, the use of anti‐(P)RR neutralizing antibodies significantly improved the regenerative ability of skeletal muscle in aged mice. Finally, we show that Yes‐associated protein (YAP) signaling, which is coordinately regulated by Wnt/β‐catenin, contributed to the development of (P)RR‐induced sarcopenia. The present study demonstrates the use of (P)RR‐Tg mice as a novel sarcopenia model, and shows that (P)RR‐Wnt‐YAP signaling plays a pivotal role in the pathogenesis of this disease. 相似文献
28.
Ridoutt Bradley Motoshita Masaharu Pfister Stephan 《The International Journal of Life Cycle Assessment》2019,24(9):1620-1630
The International Journal of Life Cycle Assessment - So far, land occupation impact assessment models in life-cycle assessment have predominantly considered biodiversity, ecosystem quality and... 相似文献
29.
Murakami Shinsuke Nakatani Jun Nakajima Kenichi Amasawa Eri Ii Ryota Hayashi Kiyotada Yoshikawa Naoki Daigo Ichiro Kishita Yusuke Ihara Tomohiko Shobatake Koichi Kudoh Yuki Motoshita Masaharu Kanemoto Keiichiro Hara Minako Kashiwagi Aiichiro Hashimoto Seiji Shigetomi Yosuke Kanzaki Masayuki Kikuchi Yasunori Ohno Hajime Fukushima Yasuhiro 《The International Journal of Life Cycle Assessment》2019,24(8):1544-1552
The International Journal of Life Cycle Assessment - 相似文献
30.
Susan K. Boehlein Peng Liu Ashley Webster Camila Ribeiro Masaharu Suzuki Shan Wu Jiahn‐Chou Guan Jon D. Stewart William F. Tracy A. Mark Settles Donald R. McCarty Karen E. Koch Larkin C. Hannah Tracie A. Hennen‐Bierwagen Alan M. Myers 《The Plant journal : for cell and molecular biology》2019,99(1):23-40