全文获取类型
收费全文 | 44253篇 |
免费 | 4136篇 |
国内免费 | 33篇 |
专业分类
48422篇 |
出版年
2022年 | 271篇 |
2021年 | 603篇 |
2020年 | 336篇 |
2019年 | 411篇 |
2018年 | 554篇 |
2017年 | 512篇 |
2016年 | 925篇 |
2015年 | 1593篇 |
2014年 | 1734篇 |
2013年 | 2203篇 |
2012年 | 2759篇 |
2011年 | 2836篇 |
2010年 | 1856篇 |
2009年 | 1792篇 |
2008年 | 2605篇 |
2007年 | 2620篇 |
2006年 | 2552篇 |
2005年 | 2519篇 |
2004年 | 2455篇 |
2003年 | 2418篇 |
2002年 | 2368篇 |
2001年 | 498篇 |
2000年 | 386篇 |
1999年 | 568篇 |
1998年 | 673篇 |
1997年 | 479篇 |
1996年 | 435篇 |
1995年 | 419篇 |
1994年 | 401篇 |
1993年 | 409篇 |
1992年 | 341篇 |
1991年 | 312篇 |
1990年 | 329篇 |
1989年 | 244篇 |
1988年 | 296篇 |
1987年 | 274篇 |
1986年 | 269篇 |
1985年 | 330篇 |
1984年 | 375篇 |
1983年 | 337篇 |
1982年 | 434篇 |
1981年 | 432篇 |
1980年 | 413篇 |
1979年 | 267篇 |
1978年 | 298篇 |
1977年 | 265篇 |
1976年 | 274篇 |
1975年 | 209篇 |
1974年 | 279篇 |
1973年 | 251篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
21.
22.
23.
Modified moving average analysis of T-wave alternans to predict ventricular fibrillation with high accuracy. 总被引:6,自引:0,他引:6
T-wave alternans is a marker of cardiac electrical instability with the potential for arrhythmia risk stratification. The modified moving average method was developed to measure alternans in settings with artifacts, noise, and nonstationary data. Algorithms were developed and performance characteristics were validated with simulated electrocardiograms (ECGs). Experimental laboratory ECGs with dynamically changing alternans values were analyzed. Alternans values estimated by modified moving average analysis correlated strongly with input alternans values (r(2) = 0.9999). Rapidly changing alternans levels and phase reversals did not perturb the measurement. When heart rate was increased from 60 to 180 beats/min, with T-wave alternans apex moving from 237 to 103 ms after the R wave, the measured alternans peak varied <5% from input value. Simulated 50- to 1,000-microV motion artifact spikes typical of treadmill ECGs produced inaccuracies <2%. Alternans values in experimental laboratory study using standard electrodes tracked vulnerability to myocardial ischemia-induced ventricular fibrillation with 100% sensitivity and specificity at a cut point of 0.75 mV. Modified moving average analysis is a robust method that precisely measures T-wave alternans in settings with artifacts, noise, and nonstationary data typical of clinical ECGs and yields an accurate estimate of risk for ventricular fibrillation. 相似文献
24.
Molecular dynamics (MD) simulations of phosphatidylinositol (4,5)-bisphosphate (PIP2) and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in 1-palmitoyl 2-oleoyl phosphatidylcholine (POPC) bilayers indicate that the inositol rings are tilted ∼40° with respect to the bilayer surface, as compared with 17° for the P-N vector of POPC. Multiple minima were obtained for the ring twist (analogous to roll for an airplane). The phosphates at position 1 of PIP2 and PIP3 are within an Ångström of the plane formed by the phosphates of POPC; lipids in the surrounding shell are depressed by 0.5-0.8 Å, but otherwise the phosphoinositides do not substantially perturb the bilayer. Finite size artifacts for ion distributions are apparent for systems of ∼26 waters/lipid, but, based on simulations with a fourfold increase of the aqueous phase, the phosphoinositide positions and orientations do not show significant size effects. Electrostatic potentials evaluated from Poisson-Boltzmann (PB) calculations show a strong dependence of potential height and ring orientation, with the maxima on the −25 mV surfaces (17.1 ± 0.1 Å for PIP2 and 19.4 ± 0.3 Å for PIP3) occurring near the most populated orientations from MD. These surfaces are well above the background height of 10 Å estimated for negatively charged cell membranes, as would be expected for lipids involved in cellular signaling. PB calculations on microscopically flat bilayers yield similar maxima as the MD-based (microscopically rough) systems, but show less fine structure and do not clearly indicate the most probable regions. Electrostatic free energies of interaction with pentalysine are also similar for the rough and flat systems. These results support the utility of a rigid/flat bilayer model for PB-based studies of PIP2 and PIP3 as long as the orientations are judiciously chosen. 相似文献
25.
26.
Sharat J. Vayttaden Jacqueline Friedman Tuan M. Tran Thomas C. Rich Carmen W. Dessauer Richard B. Clark 《PLoS computational biology》2010,6(1)
We developed a unified model of the GRK-mediated β2 adrenergic receptor (β2AR) regulation that simultaneously accounts for six different biochemical measurements of the system obtained over a wide range of agonist concentrations. Using a single deterministic model we accounted for (1) GRK phosphorylation in response to various full and partial agonists; (2) dephosphorylation of the GRK site on the β2AR; (3) β2AR internalization; (4) recycling of the β2AR post isoproterenol treatment; (5) β2AR desensitization; and (6) β2AR resensitization. Simulations of our model show that plasma membrane dephosphorylation and recycling of the phosphorylated receptor are necessary to adequately account for the measured dephosphorylation kinetics. We further used the model to predict the consequences of (1) modifying rates such as GRK phosphorylation of the receptor, arrestin binding and dissociation from the receptor, and receptor dephosphorylation that should reflect effects of knockdowns and overexpressions of these components; and (2) varying concentration and frequency of agonist stimulation “seen” by the β2AR to better mimic hormonal, neurophysiological and pharmacological stimulations of the β2AR. Exploring the consequences of rapid pulsatile agonist stimulation, we found that although resensitization was rapid, the β2AR system retained the memory of the previous stimuli and desensitized faster and much more strongly in response to subsequent stimuli. The latent memory that we predict is due to slower membrane dephosphorylation, which allows for progressive accumulation of phosphorylated receptor on the surface. This primes the receptor for faster arrestin binding on subsequent agonist activation leading to a greater extent of desensitization. In summary, the model is unique in accounting for the behavior of the β2AR system across multiple types of biochemical measurements using a single set of experimentally constrained parameters. It also provides insight into how the signaling machinery can retain memory of prior stimulation long after near complete resensitization has been achieved. 相似文献
27.
28.
During the progression of malignant peritoneal mesothelioma (MPeM), tumor nodules propagate diffusely within the abdomen and tumors are characterized by distinct phenotypic sub-types. Recent studies in solid organ cancers have shown that cancer stem cells (CSCs) play a pivotal role in the initiation and progression of tumors. However, it is not known whether tumorigenic stem cells exist and whether they promote tumor growth in MPeM. In this study, we developed and characterized a CSC model for MPeM using stably expandable tumorigenic stem cells derived from patient tumors. We found morphologically distinct populations of CSCs that divide asymmetrically or symmetrically in MPeM in vitro cell culture. The MPeM stem cells (MPeMSCs) express stem cell markers c-MYC, NES and VEGFR2 and in the presence of matrix components cells form colony spheres. MPeMSCs are multipotent, differentiate into neuronal, vascular and adipose progeny upon defined induction and the differentiating cells express lineage-specific markers such as TUBB3, an early neuronal marker; vWF, VEGFA, VEGFC and IL-8, endothelial markers; and PPARγ and FABP4, adipose markers. Xenotransplantation experiments using MPeMSCs demonstrated early tumor growth compared with parental cells. Limiting dilution experiments using MPeMSCs and endothelial lineage-induced cells derived from a single MPeMSC resulted in early tumor growth in the latter group indicating that endothelial differentiation of MPeMSCs is important for MPeM tumor initiation. Our observation that the MPeM tumors contain stem cells with tumorigenic potential has important implications for understanding the cells of origin and tumor progression in MPeM and hence targeting CSCs may be a useful strategy to inhibit malignant progression. 相似文献
29.
Richard G. Condon 《Human ecology: an interdisciplinary journal》1991,19(3):287-321
Birth seasonally at high latitudes is a complex phenomenon which is undoubtedly affected by a subtle interaction between environmental rhythmicity (most notably in photoperiod and temperature) and cultural adaption. There is intriguing evidence that human gonadotrophic activity (and hence fertility) may be affected by seasonal fluctuations in light intensity and duration. Nevertheless, cultural factors are important insofar as they mediate between environmental rhythmicity and human fertility/birth patterns. This article examines the distribution of births over several decades in an Inuit community located 300 miles north of the Arctic Circle. Several shifts in birth seasonality are noted, the most significant of which is a dramatic shift from pronounced seasonality in the 1970s to non-seasonality in the 1980s. Longitudinal ethnographic fieldwork has allowed an examination of social and economic changes accounting for the rather sudden disappearance of birth seasonality. These include increasing reliance upon wage employment and social assistance, decreased dependence upon subsistence hunting and trapping, changing attitudes on the part of young people entering their prime reproductive years, and the introduction of television, radio, and southern-style recreational activities. 相似文献
30.