全文获取类型
收费全文 | 727篇 |
免费 | 62篇 |
出版年
2021年 | 12篇 |
2020年 | 8篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 11篇 |
2016年 | 14篇 |
2015年 | 23篇 |
2014年 | 19篇 |
2013年 | 55篇 |
2012年 | 46篇 |
2011年 | 35篇 |
2010年 | 35篇 |
2009年 | 24篇 |
2008年 | 25篇 |
2007年 | 26篇 |
2006年 | 36篇 |
2005年 | 42篇 |
2004年 | 28篇 |
2003年 | 34篇 |
2002年 | 19篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 16篇 |
1998年 | 14篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1993年 | 8篇 |
1992年 | 15篇 |
1991年 | 8篇 |
1990年 | 11篇 |
1989年 | 14篇 |
1988年 | 10篇 |
1987年 | 14篇 |
1986年 | 8篇 |
1985年 | 14篇 |
1984年 | 13篇 |
1983年 | 7篇 |
1982年 | 9篇 |
1981年 | 5篇 |
1979年 | 10篇 |
1978年 | 5篇 |
1977年 | 8篇 |
1974年 | 4篇 |
1973年 | 8篇 |
1972年 | 7篇 |
1971年 | 3篇 |
1968年 | 3篇 |
1966年 | 4篇 |
1907年 | 2篇 |
排序方式: 共有789条查询结果,搜索用时 15 毫秒
31.
Clark A. Lindgren Dennis J. Paulson Michael F. Shanahan 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1982,721(4):385-393
The usefulness of isolated Ca2+-tolerant myocytes as a cellular model system for investigating modulation of monosaccharide transport by insulin was investigated. We have found that the isolation technique described by Haworth et al. (Haworth, R.A., Hunter, D.R. and Berkoff, H.A. (1980) J. Mol. Cell. Cardiol. 12, 715–724), with some minor modifications, consistently gave the highest yield of quiescent, rod-shaped myocytes which maintained their integrity in the presence of 2 mM calcium. Using 3-O-methylglucose, a non-metabolized sugar, transport was shown to possess saturability, substrate stereospecificity, competition and countertransport; all of which have been thoroughly established for d-glucose transport in other systems. The apparent Km of transport ranged from 2.3 to 3.5 mM. Insulin (10 nM) caused a small but significant increase in Km and a 2–3-fold increase in Vmax. These results suggest that this myocyte preparation will provide a useful model for studying the transport-related effects of insulin as well as current hypotheses regarding the mechanism of insulin modulation of transport at the cellular level. 相似文献
32.
33.
34.
35.
36.
Ivar Vleut Samuel Israel Levy-Tacher Willem Frederik de Boer Jorge Galindo-González Luis-Bernardo Vazquez 《PloS one》2013,8(10)
Most studies on frugivorous bat assemblages in secondary forests have concentrated on differences among successional stages, and have disregarded the effect of forest management. Secondary forest management practices alter the vegetation structure and fruit availability, important factors associated with differences in frugivorous bat assemblage structure, and fruit consumption and can therefore modify forest succession. Our objective was to elucidate factors (forest structural variables and fruit availability) determining bat diversity, abundance, composition and species-specific abundance of bats in (i) secondary forests managed by Lacandon farmers dominated by Ochroma pyramidale, in (ii) secondary forests without management, and in (iii) mature rain forests in Chiapas, Southern Mexico. Frugivorous bat species diversity (Shannon H’) was similar between forest types. However, bat abundance was highest in rain forest and O. pyramidale forests. Bat species composition was different among forest types with more Carollia sowelli and Sturnira lilium captures in O. pyramidale forests. Overall, bat fruit consumption was dominated by early-successional shrubs, highest late-successional fruit consumption was found in rain forests and more bats consumed early-successional shrub fruits in O. pyramidale forests. Ochroma pyramidale forests presented a higher canopy openness, tree height, lower tree density and diversity of fruit than secondary forests. Tree density and canopy openness were negatively correlated with bat species diversity and bat abundance, but bat abundance increased with fruit abundance and tree height. Hence, secondary forest management alters forests’ structural characteristics and resource availability, and shapes the frugivorous bat community structure, and thereby the fruit consumption by bats. 相似文献
37.
Dominik Thimm Melanie Knospe Aliaa Abdelrahman Miguel Moutinho Bernt B. A. Alsdorf Ivar von Kügelgen Anke C. Schiedel Christa E. Müller 《Purinergic signalling》2013,9(3):415-426
The nucleobase adenine has previously been reported to activate G protein-coupled receptors in rat and mouse. Adenine receptors (AdeR) thus constitute a new family of purine receptors, for which the designation “P0-receptors” has been suggested. We now describe the cloning and characterization of two new members of the AdeR family from mouse (MrgA10, termed mAde1R) and hamster (cAdeR). Both receptors were expressed in Sf9 insect cells, and radioligand binding studies were performed using [3H]adenine. Specific binding of the radioligand was detected in transfected, but not in untransfected cells, and K D values of 286 nM (mAde1R, B max 1.18 pmol/mg protein) and 301 nM (cAdeR, B max 17.7 pmol/mg protein), respectively, were determined. A series of adenine derivatives was investigated in competition binding assays. Minor structural modifications generally led to a reduction or loss of affinity, with one exception: 2-fluoroadenine was at least as potent as adenine itself at the cAdeR. Structure–activity relationships at all AdeR orthologs and subtypes investigated so far were similar, but not identical. For functional analyses, the cAdeR was homologously expressed in Chinese hamster ovary (CHO) cells, while the mAde1R was heterologously expressed in 1321N1 astrocytoma cells. Like the previously described AdeRs from rat (rAdeR) and mouse (mAde2R), the mAde1R (EC50 9.77 nM) and the cAdeR (EC50 51.6 nM) were coupled to inhibition of adenylate cyclase. In addition, the cAdeR from hamster expressed in CHO cells produced an increase in intracellular calcium concentrations (EC50 6.24 nM) and was found to be additionally coupled to Gq proteins. 相似文献
38.
Takahiro Seki Lijie Gong Aislinn J. Williams Norio Sakai Sokol V. Todi Henry L. Paulson 《The Journal of biological chemistry》2013,288(24):17145-17155
The functional diversity of deubiquitinating enzymes (DUBs) is not well understood. The MJD family of DUBs consists of four cysteine proteases that share a catalytic “Josephin” domain. The family is named after the DUB ATXN3, which causes the neurodegenerative disease Machado-Joseph disease. The two closely related Josephin domain-containing (JosD) proteins 1 and 2 consist of little more than the Josephin domain. To gain insight into the properties of Josephin domains, we investigated JosD1 and JosD2. JosD1 and JosD2 were found to differ fundamentally in many respects. In vitro, only JosD2 can cleave ubiquitin chains. In contrast, JosD1 cleaves ubiquitin chains only after it is monoubiquitinated, a form of posttranslational-dependent regulation shared with ATXN3. A significant fraction of JosD1 is monoubiquitinated in diverse mouse tissues. In cell-based studies, JosD2 localizes to the cytoplasm whereas JosD1 preferentially localizes to the plasma membrane, particularly when ubiquitinated. The membrane occupancy by JosD1 suggests that it could participate in membrane-dependent events such as cell motility and endocytosis. Indeed, time-lapse imaging revealed that JosD1 enhances membrane dynamics and cell motility. JosD1 also influences endocytosis in cultured cells by increasing the uptake of endocytic markers of macropinocytosis while decreasing those for clathrin- and caveolae-mediated endocytosis. Our results establish that two closely related DUBs differ markedly in activity and function and that JosD1, a membrane-associated DUB whose activity is regulated by ubiquitination, helps regulate membrane dynamics, cell motility, and endocytosis. 相似文献
39.
Ivar M. McDonald Robert A. Mate F. Christopher Zusi Hong Huang Debra J. Post-Munson Meredith A. Ferrante Lizbeth Gallagher Robert L. Bertekap Ronald J. Knox Barbara J. Robertson David G. Harden Daniel G. Morgan Nicholas J. Lodge Steven I. Dworetzky Richard E. Olson John E. Macor 《Bioorganic & medicinal chemistry letters》2013,23(6):1684-1688
High throughput screening led to the identification of a novel series of quinolone α7 nicotinic acetylcholine receptor (nAChR) agonists. Optimization of an HTS hit (1) led to 4-phenyl-1-(quinuclidin-3-ylmethyl)quinolin-2(1H)-one, which was found to be potent and selective. Poor brain penetrance in this series was attributed to transporter-mediated efflux, which was in turn due to high pKa. A novel 4-fluoroquinuclidine significantly lowered the pKa of the quinuclidine moiety, reducing efflux as measured by a Caco-2 assay. 相似文献
40.