全文获取类型
收费全文 | 740篇 |
免费 | 56篇 |
国内免费 | 20篇 |
专业分类
816篇 |
出版年
2023年 | 5篇 |
2022年 | 9篇 |
2021年 | 10篇 |
2020年 | 15篇 |
2019年 | 19篇 |
2018年 | 9篇 |
2017年 | 10篇 |
2016年 | 23篇 |
2015年 | 43篇 |
2014年 | 57篇 |
2013年 | 53篇 |
2012年 | 60篇 |
2011年 | 54篇 |
2010年 | 38篇 |
2009年 | 40篇 |
2008年 | 29篇 |
2007年 | 30篇 |
2006年 | 28篇 |
2005年 | 41篇 |
2004年 | 37篇 |
2003年 | 23篇 |
2002年 | 19篇 |
2001年 | 6篇 |
2000年 | 6篇 |
1999年 | 11篇 |
1998年 | 9篇 |
1997年 | 5篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 5篇 |
1992年 | 8篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 10篇 |
1988年 | 8篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 7篇 |
1980年 | 3篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1974年 | 3篇 |
1973年 | 7篇 |
1972年 | 2篇 |
1968年 | 4篇 |
排序方式: 共有816条查询结果,搜索用时 9 毫秒
11.
Cao Y Gao X Zhang W Zhang G Nguyen AK Liu X Jimenez F Cox CS Townsend CM Ko TC 《American journal of physiology. Gastrointestinal and liver physiology》2011,301(1):G156-G164
Dietary fiber intake links to decreased risk of colorectal cancers. The underlying mechanisms remain unclear. Recently, we found that butyrate, a short-chain fatty acid produced in gut by bacterial fermentation of dietary fiber, enhances TGF-β signaling in rat intestinal epithelial cells (RIE-1). Furthermore, TGF-β represses inhibitors of differentiation (Ids), leading to apoptosis. We hypothesized that dietary fiber enhances TGF-β's growth inhibitory effects on gut epithelium via inhibition of Id2. In this study, Balb/c and DBA/2N mice were fed with a regular rodent chow or supplemented with a dietary fiber (20% pectin) and Smad3 level in gut epithelium was measured. In vitro, RIE-1 cells were treated with butyrate and TGF-β(1), and cell functions were evaluated. Furthermore, the role of Ids in butyrate- and TGF-β-induced growth inhibition was investigated. We found that pectin feeding increased Smad3 protein levels in the jejunum (1.47 ± 0.26-fold, P = 0.045, in Balb/c mice; 1.49 ± 0.19-fold, P = 0.016, in DBA/2N mice), and phospho-Smad3 levels (1.92 ± 0.27-fold, P = 0.009, in Balb/c mice; 1.83 ± 0.28-fold, P = 0.022, in DBA/2N mice). Butyrate or TGF-β alone inhibited cell growth and induced cell cycle arrest. The combined treatment of butyrate and TGF-β synergistically induced cell cycle arrest and apoptosis in RIE-1 cells and repressed Id2 and Id3 levels. Furthermore, knockdown of Id2 gene expression by use of small interfering RNA caused cell cycle arrest and apoptosis. We conclude that dietary fiber pectin enhanced Smad3 expression and activation in the gut. Butyrate and TGF-β induced cell cycle arrest and apoptosis, which may be mediated by repression of Id2. Our results implicate a novel mechanism of dietary fiber in reducing the risk of colorectal cancer development. 相似文献
12.
利用聚乙二醇(PEG8000)纯化小球藻病毒FJ-1 总被引:1,自引:0,他引:1
为了提取小球藻病毒基因组DNA,探索利用3% ̄10%的PEG8000加3% ̄7%的NaCl沉淀病毒。其中以7%的PEG和4%的NaCl沉淀效果最好,但其沉淀效率较低。 相似文献
13.
Caco-2 intestinal cell differentiation is associated with G1 arrest and suppression of CDK2 and CDK4 总被引:1,自引:0,他引:1
Ding Qing-Ming; Ko Tien C.; Evers B. Mark 《American journal of physiology. Cell physiology》1998,275(5):C1193
The cellular mechanisms regulating intestinal proliferation anddifferentiation remain largely undefined. Previously, we showed anearly induction of the cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1 in Caco-2 cells, ahuman colon cancer line that spontaneously differentiates into a smallbowel phenotype. The purpose of our present study was to assess thetiming of cell cycle arrest in relation to differentiation in Caco-2cells and to examine the mechanisms responsible for CDK inactivation.Caco-2 cells undergo a relativeG1/S block and cease toproliferate at day3 postconfluency; an increase in theactivity of terminally differentiated brush-border enzymes (sucrase andalkaline phosphatase) was noted at day6 postconfluency. Cell cycle block wasassociated with suppression of both CDK2 and CDK4 activities, which areimportant for G1/S progression.Treatment of the CDK immune complexes with the detergent deoxycholate(DOC) resulted in restoration of CDK2, but not CDK4, activity atday 3 postconfluency, suggesting the presence of inhibitory protein(s)binding to the cyclin/CDK2 complex at this time point. An increasedbinding of p21Waf1/Cip1 to CDK2complexes at day3 postconfluency was noted, suggesting a potential role for p21Waf1/Cip1in CDK2 inactivation; however, immunodepletion ofp21Waf1/Cip1 from Caco-2 proteinextracts demonstrated thatp21Waf1/Cip1 is only partiallyresponsible for CDK2 suppression atday 3 postconfluency. A decrease in the cyclin E/CDK2 complex appears tocontribute to the CDK2 inactivation noted atdays6 and12 postconfluency. Taken together, ourresults suggest that multiple mechanisms contribute to CDK suppressionduring Caco-2 cell differentiation. Inhibition of CDK2 and CDK4 leadsto G1 arrest and inhibition ofproliferation that precede Caco-2 cell differentiation. 相似文献
14.
Sung RJ Lo CP Hsiao PY Tien HC 《American journal of physiology. Heart and circulatory physiology》2011,301(4):H1625-H1638
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a malignant arrhythmogenic disorder linked to mutations in the cardiac ryanodine receptor (RyR2) and calsequestrin, predisposing the young to syncope and cardiac arrest. To define the role of β-adrenergic stimulation (BAS) and to identify potential therapeutic targeted sites relating to intracellular calcium cycling, we used a Luo-Rudy dynamic ventricular myocyte model incorporated with interacting Markov models of the L-type Ca(2+) channel (I(Ca,L)) and RyR2 to simulate the heterozygous state of mouse RyR2 R4496C mutation (RyR2(R4496C+/-)) comparable with CPVT patients with RyR2 R4497C mutation. Characteristically, in simulated cells, pacing at 4 Hz or faster or pacing at 2 Hz under BAS with effects equivalent to those of isoproterenol at ≥ 0.1 μM could readily induce delayed afterdepolarizations (DADs) and DAD-mediated triggered activity (TA) in RyR2(R4496C+/-) but not in the wild-type via enhancing both I(Ca,L) and sarcoplasmic reticulum (SR) Ca(2+) ATPase (I(UP)). Moreover, with the use of steady state values of isolated endocardial (Endo), mid-myocardial (M), and epicardial (Epi) cells as initial data for conducting single cell and one-dimensional strand studies, the M cell was more vulnerable for developing DADs and DAD-mediated TA than Endo and Epi cells, and the gap junction coupling represented by diffusion coefficient (D) of ≤ 0.000766*98 cm(2)/ms was required for generating DAD-mediated TA in RyR2(R4496C+/-). Whereas individual reduction of Ca(2+) release channel of SR and Na-Ca exchanger up to 50% was ineffective, 30% or more reduction of either I(Ca,L) or I(UP) could totally suppress the inducibility of arrhythmia under BAS. Of note, 15% reduction of both I(Ca,L) and I(UP) exerted a synergistic antiarrhythmic efficacy. Findings of this model study confirm that BAS facilitates induction of ventricular tachyarrhythmias via its action on intracellular Ca(2+) cycling and a pharmacological regimen capable of reducing I(Ca,L) could be an effective adjunctive to β-adrenergic blockers for suppressing ventricular tachyarrhythmias during CPVT. 相似文献
15.
Sensitive and High Resolution Localization and Tracking of Membrane Proteins in Live Cells with BRET
Tien‐Hung Lan Qiuju Liu Chunman Li Guangyu Wu Nevin A. Lambert 《Traffic (Copenhagen, Denmark)》2012,13(11):1450-1456
Peripheral and integral membrane proteins can be located in several different subcellular compartments, and it is often necessary to determine the location of such proteins or to track their movement in living cells. Image‐based colocalization of labeled membrane proteins and compartment markers is frequently used for this purpose, but this method is limited in terms of throughput and resolution. Here we show that bioluminescence resonance energy transfer (BRET) between membrane proteins of interest and compartment‐targeted BRET partners can report subcellular location and movement of membrane proteins in live cells. The sensitivity of the method is sufficient to localize a few hundred protein copies per cell. The spatial resolution can be sufficient to determine membrane topology, and the temporal resolution is sufficient to track changes that occur in less than 1 second. BRET requires little user intervention, and is thus amenable to large‐scale experimental designs with standard instruments. 相似文献
16.
报道了越南木樨科(Oleaceae)植物1 新记录种大果素馨(Jasminum macrocarpum Merr.).该种产自越南中南部嘉来省的K’Bang, Kon Ha Nung 地区, 凭证标本保存在 HN, IBSC. 相似文献
17.
18.
Objective
To determine the frequency of lost to follow-up (LTFU) in the setting of usual care for outpatients with rheumatic diseases including RA, SLE, AS, and Ps/PsA, to explore the associated demographic factors, and to investigate the reasons for being LTFU from the original medical care.Methods
Patients registered between May 2011 and January 2014 at the rheumatology outpatient department of a medical center were included. Those who did not attend their scheduled appointment were defined as LTFU. Univariate and multivariate logistic regression were used to analyze the factors for being LTFU.Results
A total of 781 patients were enrolled, including 406 patients with RA, 174 with SLE, 136 with AS, and 65 with Ps/PsA. The frequency of LTFU was 23.9%, 25.9%, 35.3%, and 35.4%, respectively. The frequency of LTFU was significantly different between the four rheumatic diseases (p = 0.028). In multivariate logistic regression analysis, an older age increased being LTFU in the patients with RA (OR 1.02; 95% CI 1.00–1.04; p = 0.033), but reduced being LTFU in those with Ps/PsA (OR 0.96; 95% CI 0.92–0.99; p = 0.021). Female patients with SLE and Ps/PsA were more likely to be LTFU, although this did not reach statistical significance (p = 0.056 and 0.071, respectively). The most common reason for being LTFU was moving to other district hospitals from the original medical center due to convenience for the patients with RA and SLE, and stopping medication due to minimal symptoms for the patients with AS and Ps/PsA.Conclusions
The frequency of LTFU in patients with rheumatic diseases is high. Associated demographic factors included older age in RA, female gender in SLE and Ps/PsA, and younger age in Ps/PsA, with various reasons for being LTFU. Recognizing these associated factors and reasons for being LTFU may help to improve the attendance of patients and the quality of medical care. 相似文献19.
20.
Marsh K?nigs Wouter D. Weeda L. W. Ernest van Heurn R. Jeroen Vermeulen J. Carel Goslings Jan S. K. Luitse Bwee Tien Poll-Thé Anita Beelen Marleen van der Wees Rachèl J. J. K. Kemps Coriene E. Catsman-Berrevoets Jaap Oosterlaan 《PloS one》2015,10(12)