全文获取类型
收费全文 | 2236篇 |
免费 | 166篇 |
国内免费 | 2篇 |
出版年
2023年 | 10篇 |
2022年 | 14篇 |
2021年 | 47篇 |
2020年 | 42篇 |
2019年 | 47篇 |
2018年 | 54篇 |
2017年 | 42篇 |
2016年 | 68篇 |
2015年 | 100篇 |
2014年 | 82篇 |
2013年 | 160篇 |
2012年 | 169篇 |
2011年 | 200篇 |
2010年 | 128篇 |
2009年 | 110篇 |
2008年 | 151篇 |
2007年 | 158篇 |
2006年 | 133篇 |
2005年 | 131篇 |
2004年 | 116篇 |
2003年 | 91篇 |
2002年 | 98篇 |
2001年 | 12篇 |
2000年 | 11篇 |
1999年 | 12篇 |
1998年 | 17篇 |
1997年 | 18篇 |
1996年 | 8篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 16篇 |
1992年 | 9篇 |
1991年 | 5篇 |
1990年 | 12篇 |
1989年 | 9篇 |
1988年 | 5篇 |
1987年 | 10篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 9篇 |
1975年 | 6篇 |
1974年 | 3篇 |
1973年 | 8篇 |
1972年 | 3篇 |
排序方式: 共有2404条查询结果,搜索用时 78 毫秒
991.
992.
Jun Lu Suman K. Vodnala Anna-Lena Gustavsson Tomas N. Gustafsson Birger Sj?berg Henrik A. Johansson Sangit Kumar Agneta Tjernberg Lars Engman Martin E. Rottenberg Arne Holmgren 《The Journal of biological chemistry》2013,288(38):27456-27468
Trypanosoma brucei is the causing agent of African trypanosomiasis. These parasites possess a unique thiol redox system required for DNA synthesis and defense against oxidative stress. It includes trypanothione and trypanothione reductase (TryR) instead of the thioredoxin and glutaredoxin systems of mammalian hosts. Here, we show that the benzisothiazolone compound ebsulfur (EbS), a sulfur analogue of ebselen, is a potent inhibitor of T. brucei growth with a favorable selectivity index over mammalian cells. EbS inhibited the TryR activity and decreased non-protein thiol levels in cultured parasites. The inhibition of TryR by EbS was irreversible and NADPH-dependent. EbS formed a complex with TryR and caused oxidation and inactivation of the enzyme. EbS was more toxic for T. brucei than for Trypanosoma cruzi, probably due to lower levels of TryR and trypanothione in T. brucei. Furthermore, inhibition of TryR produced high intracellular reactive oxygen species. Hydrogen peroxide, known to be constitutively high in T. brucei, enhanced the EbS inhibition of TryR. The elevation of reactive oxygen species production in parasites caused by EbS induced a programmed cell death. Soluble EbS analogues were synthesized and cured T. brucei brucei infection in mice when used together with nifurtimox. Altogether, EbS and EbS analogues disrupt the trypanothione system, hampering the defense against oxidative stress. Thus, EbS is a promising lead for development of drugs against African trypanosomiasis. 相似文献
993.
994.
Michael Ingre Wessel Van Leeuwen Tomas Klemets Christer Ullvetter Stephen Hough G?ran Kecklund David Karlsson Torbj?rn ?kerstedt 《PloS one》2014,9(10)
Sleepiness and fatigue are important risk factors in the transport sector and bio-mathematical sleepiness, sleep and fatigue modeling is increasingly becoming a valuable tool for assessing safety of work schedules and rosters in Fatigue Risk Management Systems (FRMS). The present study sought to validate the inner workings of one such model, Three Process Model (TPM), on aircrews and extend the model with functions to model jetlag and to directly assess the risk of any sleepiness level in any shift schedule or roster with and without knowledge of sleep timings. We collected sleep and sleepiness data from 136 aircrews in a real life situation by means of an application running on a handheld touch screen computer device (iPhone, iPod or iPad) and used the TPM to predict sleepiness with varying level of complexity of model equations and data. The results based on multilevel linear and non-linear mixed effects models showed that the TPM predictions correlated with observed ratings of sleepiness, but explorative analyses suggest that the default model can be improved and reduced to include only two-processes (S+C), with adjusted phases of the circadian process based on a single question of circadian type. We also extended the model with a function to model jetlag acclimatization and with estimates of individual differences including reference limits accounting for 50%, 75% and 90% of the population as well as functions for predicting the probability of any level of sleepiness for ecological assessment of absolute and relative risk of sleepiness in shift systems for safety applications. 相似文献
995.
Lucia L. Senin Omar Al-Massadi Cintia Folgueira Cecilia Castelao Maria Pardo Silvia Barja-Fernandez Arturo Roca-Rivada Maria Amil Ana B. Crujeiras Tomas Garcia-Caballero Enrico Gabellieri Rosaura Leis Carlos Dieguez Uberto Pagotto Felipe F. Casanueva Luisa M. Seoane 《PloS one》2013,8(11)
Over the years, the knowledge regarding the relevance of the cannabinoid system to the regulation of metabolism has grown steadily. A central interaction between the cannabinoid system and ghrelin has been suggested to regulate food intake. Although the stomach is the main source of ghrelin and CB1 receptor expression in the stomach has been described, little information is available regarding the possible interaction between the gastric cannabinoid and ghrelin systems in the integrated control of energy homeostasis. The main objective of the present work was to assess the functional interaction between these two systems in terms of food intake using a combination of in vivo and in vitro approaches. The present work demonstrates that the peripheral blockade of the CB1 receptor by rimonabant treatment decreased food intake but only in food-deprived animals. This anorexigenic effect is likely a consequence of decreases in gastric ghrelin secretion induced by the activation of the mTOR/S6K1 intracellular pathway in the stomach following treatment with rimonabant. In support of this supposition, animals in which the mTOR/S6K1 intracellular pathway was blocked by chronic rapamycin treatment, rimonabant had no effect on ghrelin secretion. Vagal communication may also be involved because rimonabant treatment was no longer effective when administered to animals that had undergone surgical vagotomy. In conclusion, to the best of our knowledge, the present work is the first to describe a CB1 receptor-mediated mechanism that influences gastric ghrelin secretion and food intake through the mTOR pathway. 相似文献
996.
Olfactory sensitivity varies between individuals. However, data regarding cross-cultural and inter-group differences are scarce. We compared the thresholds of odor detection of the traditional society of Tsimane’ (native Amazonians of the Bolivian rainforest; n = 151) and people living in Dresden (Germany; n = 286) using “Sniffin’ Sticks” threshold subtest. Tsimane’ detected n-butanol at significantly lower concentrations than the German subjects. The distribution of thresholds of the Tsimane’ was very specific, with 25% of Tsimane’ obtaining better results in the olfactory test than any member of the German group. These data suggest that differences in olfactory sensitivity seem to be especially salient between industrialized and non-industrialized populations inhabiting different environmental conditions. We hypothesize that the possible sources of such differences are: (i) the impact of pollution which impairs the olfactory abilities of people from industrialized countries; (ii) better training of olfaction because of the higher importance of smell in traditional populations; (iii) environmental pressures shaping olfactory abilities in these populations. 相似文献
997.
998.
The time from seed germination to anthesis varied for spring wheat in experiments in climate chambers with plants grown hydroponically at different nitrogen regimes. Time to anthesis was related to the time of seed germination during the calendar year. Seed germinating earlier in the calendar year required a shorter time to anthesis compared to seed germinating later in the year, a pattern found for all the spring wheat cultivars investigated. Time to anthesis was also found to be independent of factors such as year in which the seed was produced, nitrogen regime used, or year or site of cultivation. We suggest the existence of an annual rhythm for flowering in spring wheat. This variation in time to flowering can be due either to external factors or more likely to an endogenous rhythm in the plant. When investigating plant processes, it is of importance to be aware of such a rhythm, since it may influence the results depending on when during the year the experiments are performed. 相似文献
999.
Carmelo R. Tomas 《Journal of phycology》1978,14(3):309-313
The effect of salinity and temperature on Olisthodiscus luteus Carter has been examined to across the relative importance of these factory on dynamics of natural population. A salinity range 2–50% was observed with increased tolerance to low salinity (<5%.) at higher temperature (20–30°C). Slinities at 4–5%. Had densities of 103 cells/ml?1, and growth >0.5 division day?1 at temperature of 15–30°C higher salinities (5–50%.) variable but distinct optima for density, growth and motility were observed 5, 10 and 30°C. Density and motility showed no clear optima from 10–10%.15–25°C where maximum growth rates >1.0 division/day?1 were common. Temperature increased from (0.5–1.9 division. Day?1) and increases of three orders of magnitude (102?103) for maximum densities. Temperature optima 20°C for growth 5–35%. And 25°C for >40%. were observed. The implications of these findings to natural populations of O. luleus are discussed. 相似文献
1000.
Magnus Björsne Tomas Szabó Bertil Samuelsson Björn Classon 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):279-282
Abstract In order to obtain a high degree of rigidity within the sugar moiety of nucleosides, some bicyclic pyrimidine nucleoside analogues where synthesized starting from cyclopentanone. The C-4′-substituent is fused to the C-3′-position via a propylene to give a [3.3.0]-bicyclic ring system. 相似文献