全文获取类型
收费全文 | 47578篇 |
免费 | 3195篇 |
国内免费 | 4845篇 |
专业分类
55618篇 |
出版年
2023年 | 760篇 |
2022年 | 1038篇 |
2021年 | 1168篇 |
2020年 | 1143篇 |
2019年 | 1803篇 |
2018年 | 1614篇 |
2017年 | 1310篇 |
2016年 | 1189篇 |
2015年 | 1146篇 |
2014年 | 2317篇 |
2013年 | 2928篇 |
2012年 | 1782篇 |
2011年 | 2186篇 |
2010年 | 1654篇 |
2009年 | 2165篇 |
2008年 | 2232篇 |
2007年 | 2460篇 |
2006年 | 2204篇 |
2005年 | 1800篇 |
2004年 | 1539篇 |
2003年 | 1530篇 |
2002年 | 1355篇 |
2001年 | 1175篇 |
2000年 | 972篇 |
1999年 | 849篇 |
1998年 | 813篇 |
1997年 | 772篇 |
1996年 | 752篇 |
1995年 | 750篇 |
1994年 | 739篇 |
1993年 | 649篇 |
1992年 | 653篇 |
1991年 | 641篇 |
1990年 | 496篇 |
1989年 | 507篇 |
1988年 | 457篇 |
1987年 | 441篇 |
1986年 | 427篇 |
1985年 | 678篇 |
1984年 | 905篇 |
1983年 | 729篇 |
1982年 | 760篇 |
1981年 | 610篇 |
1980年 | 618篇 |
1979年 | 545篇 |
1978年 | 437篇 |
1977年 | 410篇 |
1976年 | 373篇 |
1974年 | 244篇 |
1973年 | 258篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Xiang-Lan Sun Sarah J. Lessard Ding An Ho-Jin Koh Hiroyasu Esumi Michael F. Hirshman Laurie J. Goodyear 《Journal of cellular biochemistry》2019,120(1):685-696
The signaling mechanisms mediating myocardial glucose transport are not fully understood. Sucrose nonfermenting AMP-activated protein kinase (AMPK)-related kinase (SNARK) is an AMPK-related protein kinase that is expressed in the heart and has been implicated in contraction-stimulated glucose transport in mouse skeletal muscle. We first determined if SNARK is phosphorylated on Thr208, a site critical for SNARK activity. Mice were treated with exercise, ischemia, submaximal insulin, or maximal insulin. Treadmill exercise slightly, but significantly increased SNARK Thr208 phosphorylation. Ischemia also increased SNARK Thr208 phosphorylation, but there was no effect of submaximal or maximal insulin. HL1 cardiomyocytes were used to overexpress wild-type (WT) SNARK and to knockdown endogenous SNARK. Overexpression of WT SNARK had no effect on ischemia-stimulated glucose transport; however, SNARK knockdown significantly decreased ischemia-stimulated glucose transport. SNARK overexpression or knockdown did not alter insulin-stimulated glucose transport or glycogen concentrations. To study SNARK function in vivo, SNARK heterozygous knockout mice (SNARK+/−) and WT littermates performed treadmill exercise. Exercise-stimulated glucose transport was decreased by ~50% in hearts from SNARK+/− mice. In summary, exercise and ischemia increase SNARK Thr208 phosphorylation in the heart and SNARK regulates exercise-stimulated and ischemia-stimulated glucose transport. SNARK is a novel mediator of insulin-independent glucose transport in the heart. 相似文献
992.
Tanja Berger Ralf‐Dieter Hilgers Nicole Heussen 《Biometrical journal. Biometrische Zeitschrift》2019,61(5):1258-1269
Multiple lower limits of quantification (MLOQs) result if various laboratories are involved in the analysis of concentration data and some observations are too low to be quantified. For normally distributed data under MLOQs there exists only the multiple regression method of Helsel to estimate the mean and variance. We propose a simple imputation method and two new maximum likelihood estimation methods: the multiple truncated sample method and the multiple censored sample method. A simulation study is conducted to compare the performances of the newly introduced methods to Helsel's via the criteria root mean squared error (RMSE) and bias of the parameter estimates. Two and four lower limits of quantification (LLOQs), various amounts of unquantifiable observations and two sample sizes are studied. Furthermore, the robustness is investigated under model misspecification. The methods perform with decreasing accuracy for increasing rates of unquantified observations. Increasing sample sizes lead to smaller bias. There is almost no change in the performance between two and four LLOQs. The magnitude of the variance impairs the performance of all methods. For a smaller variance, the multiple censored sample method leads to superior estimates regarding the RMSE and bias, whereas Helsel's method is superior regarding the bias for a larger variance. Under model misspecification, Helsel's method was inferior to the other methods. Estimating the mean, the multiple censored sample method performed better, whereas the multiple truncated sample method performs best in estimating the variance. Summarizing, for a large sample size and normally distributed data we recommend to use Helsel's method. Otherwise, the multiple censored sample method should be used to obtain estimates of the mean and variance of data including MLOQs. 相似文献
993.
Richard G. Klein 《Evolutionary anthropology》2019,28(4):179-188
It has been proposed that a multiregional model could describe how Homo sapiens evolved in Africa beginning 300,000 years ago. Multiregionalism would require enduring morphological or behavioral differences among African regions and morphological or behavioral continuity within each. African fossils, archeology, and genetics do not comply with either requirement and are unlikely to, because climatic change periodically disrupted continuity and reshuffled populations. As an alternative to multiregionalism, I suggest that reshuffling produced novel gene constellations, including one in which the additive or cumulative effect of newly associated genes enhanced cognitive or communicative potential. Eventual fixation of such a constellation in the lineage leading to modern H. sapiens would explain the abrupt appearance of the African Later Stone Age 50–45 thousand years ago, its nearly simultaneous expansion to Eurasia in the form of the Upper Paleolithic, and the ability of fully modern Upper Paleolithic people to swamp or replace non‐modern Eurasians. 相似文献
994.
995.
PH(pleckstrin homology)结构域与细胞方向感觉关系密切,目前已发现,PH结构域存在于60多种蛋白质中,这些蛋白质能与趋化细胞胞膜表面的相关结合位点结合,进而激发信号转导的下游事件.这种结合有以下特点:a.迅速而短暂;b.只与外界环境中两点间浓度梯度差相关,据此提出了“空间模式”;c.改变趋化剂的位置时,结合位点在胞膜上的分布也随之改变,由此提出了“时间模式”.深入而全面地探讨各种PH结构域及其结合位点在细胞方向感觉中的作用,对于细胞方向感觉的研究具有巨大的推动作用和深远的理论意义. 相似文献
996.
热带次生林林窗干热季光照特征初步分析 总被引:17,自引:0,他引:17
利用西双版纳干热季 ( 3~ 4月 )次生林林窗光照观测资料 ,探讨了林窗光照的时空变化特征。结果表明 :由于天气现象 (雾 )、太阳高度和林窗树木的共同影响 ,使得林窗区域光照强度在时空上均存在明显的差异 ;上午光照强度的时间变化不明显 ,光强高值区在林窗西南侧边缘 ;中午受太阳辐射的影响 ,各测点光强均迅速上升 ,尤以林窗偏东侧林缘最为突出 ,实际林窗边缘的光强远远大于扩展林窗边缘 ;平均光强最大区域由林窗西南侧向东北侧林缘移动 ,而林窗偏西侧受树木遮蔽影响 ,光强虽有增加 ,但由于实际林窗边缘的高光强维持时间较短 ,平均光强较小 ,特别是偏西侧的扩展林窗边缘 ,遮蔽影响较大 ,各时刻的光强均不大 ,形成平均光强的低值区 ;使得中午林窗区域光照强度不对称性更加显著 ,光强水平梯度增大 ;下午由于太阳西进 ,林窗区域均受到树木遮蔽影响 ,光强降低 ,水平梯度变化趋于和缓。在西双版纳干热季作为林窗主要热力作用面之一的林窗地表面 ,在不同时段其最大光强的数值和出现区域以及高光强维持时期均存在较大差异 ;使得林窗区域的光强分布存在时间差异和空间不对称性 ,如此的光强分布势必造成林窗不同区域热力作用的不同 ,进而导致林窗区域热量传输和热量储存的不同 ,产生不同的热力效应。本研究结果? 相似文献
997.
Elisa Giovannetti Leticia G. Leon Valentina E. Gómez Paolo A. Zucali Filippo Minutolo 《Nucleosides, nucleotides & nucleic acids》2016,35(10-12):643-651
ABSTRACTMalignant pleural mesothelioma (MPM) is a very hypoxic malignancy, and hypoxia has been associated with resistance towards gemcitabine. The muscle-isoform of lactate dehydrogenase (LDH-A) constitutes a major checkpoint for the switch to anaerobic glycolysis. Therefore we investigated the combination of a new LDH-A inhibitor (NHI-1) with gemcitabine in MPM cell lines. Under hypoxia (O2 tension of 1%) the cell growth inhibitory effects of gemcitabine, were reduced, as demonstrated by a 5- to 10-fold increase in IC50s. However, the simultaneous addition of NHI-1 was synergistic (combination index < 1). Flow cytometry demonstrated that hypoxia caused a G1 arrest, whereas the combination of NHI-1 significantly increased gemcitabine-induced cell death. Finally, the mRNA expression levels of the human equilibrative transporter-1 (hENT1) were significantly down-regulated under hypoxia, but treatment with NHI-1 was associated with a recovery of hENT1 expression. In conclusion, our data show that hypoxia increased MPM resistance to gemcitabine. However, cell death induction and modulation of the key transporter in gemcitabine uptake may contribute to the synergistic interaction of gemcitabine with the LDH-A inhibitor NHI-1 and support further studies for the rational development of this combination. 相似文献
998.
Mutations in the E1a gene of type 5 adenovirus result in oncogenic transformation of Fischer rat embryo cells 总被引:1,自引:0,他引:1
G J Duigou L E Babiss W S Liaw S G Zimmer H S Ginsberg P B Fisher 《Journal of cellular biochemistry》1987,33(2):117-126
Transformation of a specific clone of Fischer rat embryo (CREF) cells with wild-type 5 adenovirus (Ad5) or the E1a plus E1b transforming gene regions of Ad5 results in epithelioid transformants that grow efficiently in agar but that do not induce tumors when inoculated into nude mice or syngeneic Fischer rats. In contrast, CREF cells transformed by a host-range Ad5 mutant, H5hrl, which contains a single base-pair deletion of nucleotide 1055 in E1a resulting in a 28-kd protein (calculated) in place of the wild-type 51-kd acidic protein, display a cold-sensitive transformation phenotype and an incomplete fibroblastic morphology but surprisingly do induce tumors in nude mice and syngeneic rats. Tumors develop in both types of animals following injection of CREF cells transformed by other cold-sensitive Ad5 E1a mutants (H5dl101 and H5in106), which contain alterations in their 13S mRNA and consequently truncated 289AA proteins. CREF cells transformed with only the E1a gene (0-4.5 m.u.) from H5hrl or H5dl101 also produce tumors in these animals. To directly determine the role of the 13S E1a encoded 289AA protein and the 12S E1a encoded 243AA protein in initiating an oncogenic phenotype in adenovirus-transformed CREF cells, we generated transformed cell lines following infection with the Ad2 mutant pm975, which synthesizes the 289AA E1a protein but not the 243AA protein, and the Ad5 mutant H5dl520 and the Ad2 mutant H2dl1500, which do not produce the 289AA E1a protein but synthesize the normal 243AA E1a protein. All three types of mutant adenovirus-transformed CREF cells induced tumors in nude mice and syngeneic rats. Tumor formation by these mutant adenovirus-transformed CREF cells was not associated with changes in the arrangement of integrated adenovirus DNA or in the expression of adenovirus early genes. These results indicate, therefore, that oncogenic transformation of CREF cells can occur in the presence of a wild-type 13S E1a protein or a wild-type 12S E1a protein when either protein is present alone, but does not occur when both wild-type E1a proteins are present. 相似文献
999.
1000.