全文获取类型
收费全文 | 4097篇 |
免费 | 478篇 |
专业分类
4575篇 |
出版年
2021年 | 40篇 |
2019年 | 39篇 |
2018年 | 48篇 |
2016年 | 65篇 |
2015年 | 106篇 |
2014年 | 133篇 |
2013年 | 154篇 |
2012年 | 171篇 |
2011年 | 184篇 |
2010年 | 113篇 |
2009年 | 86篇 |
2008年 | 168篇 |
2007年 | 151篇 |
2006年 | 129篇 |
2005年 | 131篇 |
2004年 | 119篇 |
2003年 | 107篇 |
2002年 | 126篇 |
2001年 | 116篇 |
2000年 | 145篇 |
1999年 | 113篇 |
1998年 | 59篇 |
1997年 | 46篇 |
1996年 | 48篇 |
1995年 | 45篇 |
1994年 | 43篇 |
1993年 | 36篇 |
1992年 | 76篇 |
1991年 | 82篇 |
1990年 | 93篇 |
1989年 | 94篇 |
1988年 | 76篇 |
1987年 | 86篇 |
1986年 | 70篇 |
1985年 | 86篇 |
1984年 | 66篇 |
1983年 | 53篇 |
1982年 | 48篇 |
1981年 | 46篇 |
1979年 | 56篇 |
1978年 | 51篇 |
1977年 | 46篇 |
1976年 | 45篇 |
1975年 | 57篇 |
1974年 | 38篇 |
1973年 | 55篇 |
1972年 | 66篇 |
1971年 | 43篇 |
1970年 | 50篇 |
1969年 | 41篇 |
排序方式: 共有4575条查询结果,搜索用时 0 毫秒
101.
Rosamarie Frieri William Fisher Rosenberger Nancy Flournoy Zhantao Lin 《Biometrics》2023,79(3):2565-2576
When there is a predictive biomarker, enrichment can focus the clinical trial on a benefiting subpopulation. We describe a two-stage enrichment design, in which the first stage is designed to efficiently estimate a threshold and the second stage is a “phase III-like” trial on the enriched population. The goal of this paper is to explore design issues: sample size in Stages 1 and 2, and re-estimation of the Stage 2 sample size following Stage 1. By treating these as separate trials, we can gain insight into how the predictive nature of the biomarker specifically impacts the sample size. We also show that failure to adequately estimate the threshold can have disastrous consequences in the second stage. While any bivariate model could be used, we assume a continuous outcome and continuous biomarker, described by a bivariate normal model. The correlation coefficient between the outcome and biomarker is the key to understanding the behavior of the design, both for predictive and prognostic biomarkers. Through a series of simulations we illustrate the impact of model misspecification, consequences of poor threshold estimation, and requisite sample sizes that depend on the predictive nature of the biomarker. Such insight should be helpful in understanding and designing enrichment trials. 相似文献
102.
103.
The structure and function of p55PIK reveal a new regulatory subunit for phosphatidylinositol 3-kinase. 总被引:8,自引:2,他引:6 下载免费PDF全文
S Pons T Asano E Glasheen M Miralpeix Y Zhang T L Fisher M G Myers Jr X J Sun M F White 《Molecular and cellular biology》1995,15(8):4453-4465
Phosphatidylinositol 3-kinase (PI-3 kinase) is implicated in the regulation of diverse cellular processes, including insulin-stimulated glucose transport. PI-3 kinase is composed of a 110-kDa catalytic subunit and an 85-kDa regulatory subunit. Here, we describe p55PIK, a new regulatory subunit that was isolated by screening expression libraries with tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1). p55PIK is composed of a unique 30-residue NH2 terminus followed by a proline-rich motif and two Src homology 2 (SH2) domains with significant sequence identify to those in p85. p55PIK mRNA is expressed early during development, remains abundant in adult mouse brain and testis tissue, and is detectable in adult adipocytes and heart and kidney tissues. p55PIK forms a stable complex with p110, and it associates with IRS-1 during insulin stimulation. Moreover, the activated insulin receptor phosphorylates p55PIK in Sf9 cells, and insulin stimulates p55PIK phosphorylation in CHOIR/p55PIK cells. The unique features of p55PIK suggest that it is important in receptor signaling. 相似文献
104.
105.
The Bacillus subtilis ureABC operon encodes homologs of the three subunits of urease enzymes of the family Enterobacteriaceae. Disruption of ureC prevented utilization of urea as a nitrogen source and resulted in a partial growth defect in minimal medium containing limiting amounts of arginine or allantoin as the sole nitrogen source. 相似文献
106.
Oxidant Injury in PC12 Cells—A Possible Model of Calcium "Dysregulation" in Aging: I. Selectivity of Protection Against Oxidative Stress 总被引:1,自引:1,他引:0
Abstract: Previous research has suggested that the initial effects of cellular free radical neurotoxic insult involve large increases in intracellular Ca2+. However, the exact role of oxidative stress on the various parameters involved in these increases has not been specified. The present experiments were performed to examine these parameters in PC12 cells exposed to 5, 25, or 300 µM H2O2 for 30 min in growth medium alone or containing either nifedipine (L-type Ca2+ antagonist), conotoxin (N-type antagonist), Trolox (vitamin E analogue), or α-phenyl-n-tert-butylnitrone (nitrone trapping agent; PBN). The concentrations of H2O2 were chosen by examining the degree of cell killing induced by exposure to graded concentrations of H2O2. The 5 and 25 µM concentrations of H2O2 produced no significant cell killing at either 30 min or 24 h after treatment, whereas the 300 µM concentration produced a moderate degree of cell killing that did not increase between the two times. Fluorescent imaging was used to visualize intracellular Ca2+ changes in fura-2-loaded cells. Baseline (pre-30 mM KCI) Ca2+ levels were increased significantly by H2O2 treatment (e.g., 300 µM, 200%), but the rise in the level of free intracellular Ca2+ after KCI stimulation (i.e., peak) was decreased (e.g., 300 µM, 50%) and the cell's ability to sequester or extrude the excess Ca2+ (i.e., Ca2+ recovery time) after depolarization was decreased significantly. All compounds prevented baseline Ca2+ increases and, with the exception of conotoxin, antagonized the peak decreases in Ca2+. It is interesting that after 300 µM H2O2 exposure, only Trolox was partially effective in preventing these deficits in recovery. Conotoxin increased the decrement recovery in the absence of H2O2. However, in cells exposed to 5 or 25 µM H2O2, conotoxin as well as the other agents were effective in preventing the deficits in recovery. 相似文献
107.
108.
The muscle layer of the canine gallbladder wall and cystic duct was found to be a three-dimensional meshwork of smooth muscle bundles which appear loosely and irregularly arranged on the mucosal aspect and consolidate to form a homogeneous plate-like layer on the serosal aspect. The muscle bundles are tightly woven around interspersed pockets of loose connective tissue in the gallbladder wall and gradually become loosely arranged with more prominent amounts of intervening connective tissue in the cystic duct. The muscle layer is thickest in the gallbladder wall and becomes progressively thinner out into the cystic duct. No anatomic sphincter was observed. Ultrastructural organization revealed individual muscle fibers to be of irregular profile, often branching, widely spaced with intervening collagen fibers, and having few cell-to-cell contacts. 相似文献
109.
Hybrid recombinant human leukocyte interferon inhibits differentiation in murine B-16 melanoma cells 总被引:1,自引:0,他引:1
P B Fisher H Hermo D R Prignoli I B Weinstein S Pestka 《Biochemical and biophysical research communications》1984,119(1):108-115
We have investigated the effects of recombinant human leukocyte interferons (IFN-alpha A and IFN-alpha D) and various hybrid recombinant human leukocyte interferons on differentiation in B-16 mouse melanoma cells. Inhibition of both spontaneous and melanocyte hormone stimulated differentiation was observed with one hybrid construct, IFN-alpha A/D (Bgl) consisting of amino acids 1 to 62 from IFN-alpha A and amino acids 64 to 166 from IFN-alpha D. In contrast, the parental human interferons, IFN-alpha A and IFN-alpha D, when used alone or in combination, as well as other hybrid human leukocyte interferons, did not cause significant inhibition of melanogenesis in B-16 mouse cells. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) also inhibited B-16 differentiation and the combination of TPA with IFN-alpha A/D (Bgl) or mouse L-cell interferon was synergistic in delaying melanogenesis. These studies indicate that the IFN-alpha A/D (Bgl) hybrid that exhibits antiviral activity on mouse cells can also inhibit differentiation of murine cells. 相似文献
110.