全文获取类型
收费全文 | 6343篇 |
免费 | 660篇 |
国内免费 | 5篇 |
出版年
2021年 | 108篇 |
2020年 | 63篇 |
2019年 | 61篇 |
2018年 | 115篇 |
2017年 | 72篇 |
2016年 | 144篇 |
2015年 | 203篇 |
2014年 | 232篇 |
2013年 | 309篇 |
2012年 | 374篇 |
2011年 | 339篇 |
2010年 | 209篇 |
2009年 | 173篇 |
2008年 | 268篇 |
2007年 | 300篇 |
2006年 | 278篇 |
2005年 | 275篇 |
2004年 | 254篇 |
2003年 | 216篇 |
2002年 | 203篇 |
2001年 | 151篇 |
2000年 | 187篇 |
1999年 | 148篇 |
1998年 | 76篇 |
1997年 | 96篇 |
1996年 | 65篇 |
1995年 | 80篇 |
1994年 | 53篇 |
1993年 | 53篇 |
1992年 | 79篇 |
1991年 | 90篇 |
1990年 | 98篇 |
1989年 | 90篇 |
1988年 | 82篇 |
1987年 | 75篇 |
1986年 | 78篇 |
1985年 | 87篇 |
1984年 | 71篇 |
1983年 | 71篇 |
1982年 | 52篇 |
1981年 | 62篇 |
1979年 | 57篇 |
1978年 | 57篇 |
1977年 | 49篇 |
1976年 | 42篇 |
1975年 | 50篇 |
1974年 | 46篇 |
1973年 | 50篇 |
1972年 | 42篇 |
1969年 | 45篇 |
排序方式: 共有7008条查询结果,搜索用时 15 毫秒
1.
2.
3.
4.
Ryota Masuzaki Sophia Zhao M. Todd Valerius Daisuke Tsugawa Yuki Oya Kevin C. Ray Seth J. Karp 《The Journal of biological chemistry》2016,291(7):3346-3358
After significant injury, the liver must maintain homeostasis during the regenerative process. We hypothesized the existence of mechanisms to limit hepatocyte proliferation after injury to maintain metabolic and synthetic function. A screen for candidates revealed suppressor of cytokine signaling 2 (SOCS2), an inhibitor of growth hormone (GH) signaling, was strongly induced after partial hepatectomy. Using genetic deletion and administration of various factors we investigated the role of SOCS2 during liver regeneration. SOCS2 preserves liver function by restraining the first round of hepatocyte proliferation after partial hepatectomy by preventing increases in growth hormone receptor (GHR) via ubiquitination, suppressing GH pathway activity. At later times, SOCS2 enhances hepatocyte proliferation by modulating a decrease in serum insulin-like growth factor 1 (IGF-1) that allows GH release from the pituitary. SOCS2, therefore, plays a dual role in modulating the rate of hepatocyte proliferation. In particular, this is the first demonstration of an endogenous mechanism to limit hepatocyte proliferation after injury. 相似文献
5.
Nicole Guthrie Andrew Bradlyn Sharon K. Thompson Sophia Yen Jana Haritatos Fred Dillon Steve W. Cole 《PloS one》2015,10(5)
Most adolescents do not achieve the recommended levels of moderate-to-vigorous physical activity (MVPA), placing them at increased risk for a diverse array of chronic diseases in adulthood. There is a great need for scalable and effective interventions that can increase MVPA in adolescents. Here we report the results of a measurement validation study and a preliminary proof-of-concept experiment testing the impact of Zamzee, an accelerometer-linked online intervention system that combines proximal performance feedback and incentive motivation features to promote MVPA. In a calibration study that parametrically varied levels of physical activity in 31 12-14 year-old children, the Zamzee activity meter was shown to provide a valid measure of MVPA (sensitivity in detecting MVPA = 85.9%, specificity = 97.5%, and r = .94 correspondence with the benchmark RT3 accelerometer system; all p < .0001). In a subsequent randomized controlled multi-site experiment involving 182 middle school-aged children assessed for MVPA over 6 wks, intent-to-treat analyses found that those who received access to the Zamzee intervention had average MVPA levels 54% greater than those of a passive control group (p < 0.0001) and 68% greater than those of an active control group that received access to a commercially available active videogame (p < .0001). Zamzee’s effects on MVPA did not diminish significantly over the course of the 6-wk study period, and were statistically significant in both females and males, and in normal- vs. high-BMI subgroups. These results provide promising initial indications that combining the Zamzee activity meter with online proximal performance feedback and incentive motivation features can positively impact MVPA levels in adolescents. 相似文献
6.
Amanda L. McGuire Sophia C. Bennett Sally M. Lansley Natalia D. Popowicz Julius F. Varano della Vergiliana Daniel Wong Y. C. Gary Lee Aron Chakera 《PloS one》2015,10(3)
A major complication of peritoneal dialysis is the development of peritonitis, which is associated with reduced technique and patient survival. The inflammatory response elicited by infection results in a fibrin and debris-rich environment within the peritoneal cavity, which may reduce the effectiveness of antimicrobial agents and predispose to recurrence or relapse of infection. Strategies to enhance responses to antimicrobial agents therefore have the potential to improve patient outcomes. This study presents pre-clinical data describing the compatibility of tPA and DNase in combination with antimicrobial agents used for the treatment of PD peritonitis. tPA and DNase were stable in standard dialysate solution and in the presence of antimicrobial agents, and were safe when given intraperitoneally in a mouse model with no evidence of local or systemic toxicity. Adjunctive tPA and DNase may have a role in the management of patients presenting with PD peritonitis. 相似文献
7.
Treatment of nonmucoid Pseudomonas aeruginosa with gyrase inhibitors such as ciprofloxacin, norfloxacin, and ofloxacin, which target the A subunit of topoisomerase II,
resulted in 100% conversion to the mucoid phenotype. However, antibiotics that partially inhibited growth and macromolecular
synthesis (DNA, RNA, protein, or peptidoglycan) of nonmucoid isolates in a gluconate-limited chemostat culture system did
not promote conversion to mucoid subpopulations. An increase in resistance was observed in populations that expressed the
mucoid phenotype. Both mucoid conversion and antibiotic resistance were completely reversible when ciprofloxacin pressure
was withdrawn, but only partially reversible by the removal of norfloxacin and ofloxacin. Thus, these experiments indicate
that in the presence of some fluoroquinolones, a conditional response resulting in mucoid conversion and antibiotic resistance
may occur.
Received: 28 January 1997 / Accepted: 12 February 1997 相似文献
8.
High purity preparations of higher plant vacuolar H+-ATPase reveal additional subunits. Revised subunit composition 总被引:16,自引:0,他引:16
A fast protein liquid chromatography procedure for purification of the V-type H+-ATPase from higher plant vacuolar membrane to yield near-homogeneous enzyme with a specific activity of 20-25 mumol/mg.min is described. When precautions are taken to ensure the quantitative recovery of protein before sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the preparation is found to be constituted of seven major polypeptides of 100, 67, 55, 52, 44, 32, and 16 kDa, respectively, and two minor components of 42 and 29 kDa. The 52-, 44-, and 32-kDa polypeptides do not cross-react with antisera raised to the 67- and 55-kDa subunits of the enzyme, and two independent sample preparation procedures yield the same apparent subunit composition. The additional polypeptides are not breakdown products or aggregates of the previously identified subunits of the ATPase. The ATPase of tonoplast vesicles is subject to MgATP-dependent cold inactivation, and the conditions for inactivation are identical to those for the bovine chromaffin granule H+-ATPase (Moriyama, Y., and Nelson, N. (1989) J. Biol. Chem. 264, 3577-3582). Cold inactivation is accompanied by the detachment of five major polypeptides of 67, 55, 52, 44, and 32 kDa from the membrane, and all five components co-migrate with the corresponding polypeptides of the purified ATPase upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 100- and 16-kDa polypeptides of the ATPase are not removed from the membrane during cold inactivation, but the latter can be purified to homogeneity by chloroform:methanol extraction of the fast protein liquid chromatography-purified enzyme. It is concluded that the tonoplast H+-ATPase is constituted of 6-7 major polypeptides organized into a peripheral sector comprising the 67-, 55-, 52-, 44-, and 32-kDa components and an integral sector consisting of the 100- and 16-kDa polypeptides. The V-type H+-ATPase from animal endomembranes and higher plant vacuolar membranes therefore have remarkably similar subunit compositions and gross topographies. 相似文献
9.
10.
Breast muscle of young chicks fed chow diets containing the creatine analog 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine) accumulated up to 40 mumol/g wet weight of the synthetic phosphagen 1-carboxymethyl-2-imino-3-phosphonoimidazolidine (cyclocreatine-P2-). ATP levels were sustained at high values substantially longer in breast muscle of cyclocreatine-fed chicks, compared to control-fed chicks, during total ischemia initiated 2 h after injection of both groups with the beta-adrenergic agonist isoproterenol (5 mg/kg subcutaneous). For example, in chicks fed 0.5% cyclocreatine for 10-19 days ATP levels in isoproterenol-stimulated breast muscles after 1 h of ischemia at 37 degrees C were 6.1 mumol/g, compared to 1.9 mumol/g for the control-fed group, and after 2 h of ischemia were 3.5 mumol/g compared to 0.6 mumol/g for controls. Creatine-P reserves in isoproterenol-stimulated breast muscles of all dietary groups were essentially exhausted within the first hour of ischemia. In contrast, breast muscle of chicks fed either 1 or 0.5% cyclocreatine still contained 28 and 19 mumol/g of cyclocreatine-P, respectively, after 1 h of ischemia; after 2 h of ischemia, the respective cyclocreatine-P values were 20 and 13 mumol/g. Isoproterenol-stimulated chick breast muscle provides the first skeletal muscle model system for studying the molecular mechanisms by which dietary cyclocreatine helps sustain ATP levels during ischemia. Although adaptive factors are also involved, it is suggested that a significant portion of the ATP-sustaining activity of dietary cyclocreatine in ischemic breast muscle can be attributed to the unique thermodynamic properties of the accumulated cyclocreatine-P. These properties enable cyclocreatine-P to continue to thermodynamically buffer the adenylate system and transport high energy phosphate throughout the long muscle fibers at cytosolic pH values and phosphorylation potentials well below the range where the creatine-P system can function effectively. Synergism between glycolysis and this long-acting synthetic phosphagen might well help delay depletion of ATP levels in skeletal muscles during ischemia. Cyclocreatine feeding provides a unique experimental tool for quantitative evaluation of the proposed protective role of ATP against irreversible cellular damage in skeletal and cardiac muscles during ischemic episodes. 相似文献