全文获取类型
收费全文 | 519篇 |
免费 | 65篇 |
出版年
2022年 | 6篇 |
2021年 | 17篇 |
2019年 | 6篇 |
2018年 | 23篇 |
2017年 | 5篇 |
2016年 | 12篇 |
2015年 | 27篇 |
2014年 | 28篇 |
2013年 | 29篇 |
2012年 | 35篇 |
2011年 | 33篇 |
2010年 | 15篇 |
2009年 | 15篇 |
2008年 | 27篇 |
2007年 | 29篇 |
2006年 | 26篇 |
2005年 | 17篇 |
2004年 | 30篇 |
2003年 | 16篇 |
2002年 | 10篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1992年 | 5篇 |
1991年 | 11篇 |
1990年 | 9篇 |
1989年 | 11篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 9篇 |
1984年 | 6篇 |
1983年 | 8篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 7篇 |
1975年 | 5篇 |
1974年 | 11篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1971年 | 4篇 |
1970年 | 3篇 |
1967年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有584条查询结果,搜索用时 15 毫秒
71.
Michael R. Tadross Manu Ben Johny David T. Yue 《The Journal of general physiology》2010,135(3):197-215
Ca2+/calmodulin- and voltage-dependent inactivation (CDI and VDI) comprise vital prototypes of Ca2+ channel modulation, rich with biological consequences. Although the events initiating CDI and VDI are known, their downstream mechanisms have eluded consensus. Competing proposals include hinged-lid occlusion of channels, selectivity filter collapse, and allosteric inhibition of the activation gate. Here, novel theory predicts that perturbations of channel activation should alter inactivation in distinctive ways, depending on which hypothesis holds true. Thus, we systematically mutate the activation gate, formed by all S6 segments within CaV1.3. These channels feature robust baseline CDI, and the resulting mutant library exhibits significant diversity of activation, CDI, and VDI. For CDI, a clear and previously unreported pattern emerges: activation-enhancing mutations proportionately weaken inactivation. This outcome substantiates an allosteric CDI mechanism. For VDI, the data implicate a “hinged lid–shield” mechanism, similar to a hinged-lid process, with a previously unrecognized feature. Namely, we detect a “shield” in CaV1.3 channels that is specialized to repel lid closure. These findings reveal long-sought downstream mechanisms of inactivation and may furnish a framework for the understanding of Ca2+ channelopathies involving S6 mutations. 相似文献
72.
Optical rotatory dispersion measurements were used to follow the transition from the helical to the random coil conformation of poly-β-benzyl-L -aspartate as induced by changes in temperature and solvent composition in mixtures of dioxane and dimethylsulfoxide. Within experimental error, there is no difference in the stability of the helical state as measured in this way for the protonated and deuterated forms of the polypeptide. This result is considered in terms of previous attempts to study the isotope effect on conformational transitions of helical biological macromolecules and polypeptides. The conclusion is drawn that the apparent changes in conformational stability observed in these previous systems arise from alteration of the properties of the solvent. Speculations are advanced regarding the contribution of the interpeptide bond to the stability of the helical state. 相似文献
73.
The ribosomal subunits of hamster cell mitochondria 总被引:2,自引:0,他引:2
74.
A Kh Kogan N I Losev A B Tsypin B M Manu?lov 《Biulleten' eksperimental'no? biologii i meditsiny》1989,107(6):688-690
In experiments on dogs using the chemiluminescent method and nitroblue-tetrazole reaction the authors found out that leucocytes while passing through the pulmonary vessels bed, in contrast to the spleen increase the generation of active microbicidal forms of oxygen. Due to this fact we suppose that the lungs may take part in the formation of free radical status and phagocytic antiinfectious defence of the organism. 相似文献
75.
76.
The 5′ sequence of Sindbis viral RNA is m 7G5′ pppApUpGp... 相似文献
77.
Muhammad Furqan Bari Martin O. Weickert Kavitha Sivakumar Sean G. James David R. J. Snead Bee Kang Tan Harpal Singh Randeva Claire Cecile Bastie Manu Vatish 《PloS one》2014,9(7)
Recently soluble CD163 (sCD163), a cleaved form of the macrophage receptor CD163, was identified as a macrophage-specific risk-predictor for developing Type 2 Diabetes. Here, we investigate circulating levels of sCD163 in gestational diabetes mellitus (GDM). Furthermore, given the role of the placenta in the pathogenesis of GDM, we assessed placental contribution to sCD163 secretion. Paired maternal (venous) and umbilical vein blood samples from GDM (n = 18) and Body Mass Index (BMI) matched control women (n = 20) delivered by caesarean section at 39–40 week gestation were assessed for circulating levels of sCD163, Tumour necrosis factor alpha (TNF-α) and Interleukin 6 (IL-6). Media from explant culture of maternal subcutaneous fat and corresponding placental tissues were assayed for these same molecules. CD163 positive cell numbers were determined in placental and adipose tissues of GDM and control women. We found significantly elevated circulating sCD163 levels in GDM mothers (688.4±46.9 ng/ml vs. 505.6±38.6 ng/ml) and their offspring (418.2±26.6 ng/ml vs. 336.3±24.4 ng/ml [p<0.05 for both]) as compared to controls, together with elevated circulating TNF-α and IL-6 levels. Moreover, both GDM placentae (268.1±10.8 ng/ml/mg vs. 187.6±20.6 ng/ml/mg) and adipose explants (41.1±2.7 ng/ml/mg vs. 26.6±2.4 ng/ml/mg) released significantly more sCD163 than controls. Lastly, significantly more CD163 positive cells were observed in GDM placentae (25.7±1.1 vs. 22.1±1.2) and adipose tissue (19.1±1.1 vs 12.7±0.9) compared to controls. We describe elevated sCD163 levels in GDM and identify human placenta as a novel source of sCD163 suggesting that placental tissues might contribute to the increased levels of circulating sCD163 in GDM pregnancies. 相似文献
78.
BackgroundClinical outcome prediction normally employs static, one-size-fits-all models that perform well for the average patient but are sub-optimal for individual patients with unique characteristics. In the era of digital healthcare, it is feasible to dynamically personalize decision support by identifying and analyzing similar past patients, in a way that is analogous to personalized product recommendation in e-commerce. Our objectives were: 1) to prove that analyzing only similar patients leads to better outcome prediction performance than analyzing all available patients, and 2) to characterize the trade-off between training data size and the degree of similarity between the training data and the index patient for whom prediction is to be made.ConclusionsThe present study provides crucial empirical evidence for the promising potential of personalized data-driven decision support systems. With the increasing adoption of electronic medical record (EMR) systems, our novel medical data analytics contributes to meaningful use of EMR data. 相似文献
79.
Michael G. Thomas Manu De Rycker Ignacio Cotillo Torrejon John Thomas Jennifer Riley Daniel Spinks Kevin D. Read Tim J. Miles Ian H. Gilbert Paul G. Wyatt 《Bioorganic & medicinal chemistry letters》2018,28(18):3025-3030
Chagas’ disease, caused by the protozoan parasite Trypanosoma cruzi, affects 8–10 million people across the Latin American population and is responsible for around 12,500 deaths per annum. The current frontline treatments, benznidazole and nifurtimox, are associated with side effects and lack efficacy in the chronic stage of the disease, leading to an urgent need for new treatments. A high throughput screening campaign against the physiologically relevant intracellular form of the parasite identified a series of 2,4-diamino-6-methylpyrimidines. Demonstrating the series did not work through the anti-target TcCYP51, and was generally cytocidal, confirmed its suitability for further development. This study reports the optimisation of selectivity and metabolic stability of the series and identification of a suitable lead for further optimisation. 相似文献
80.