全文获取类型
收费全文 | 257篇 |
免费 | 37篇 |
专业分类
294篇 |
出版年
2022年 | 4篇 |
2021年 | 7篇 |
2020年 | 8篇 |
2019年 | 7篇 |
2018年 | 11篇 |
2017年 | 7篇 |
2016年 | 7篇 |
2015年 | 17篇 |
2014年 | 13篇 |
2013年 | 13篇 |
2012年 | 23篇 |
2011年 | 17篇 |
2010年 | 7篇 |
2009年 | 9篇 |
2008年 | 15篇 |
2007年 | 15篇 |
2006年 | 8篇 |
2005年 | 9篇 |
2004年 | 9篇 |
2003年 | 5篇 |
2002年 | 3篇 |
2001年 | 5篇 |
2000年 | 7篇 |
1999年 | 2篇 |
1997年 | 4篇 |
1994年 | 4篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1987年 | 2篇 |
1985年 | 3篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1964年 | 1篇 |
1952年 | 1篇 |
1936年 | 1篇 |
排序方式: 共有294条查询结果,搜索用时 15 毫秒
1.
2.
3.
Gregory J. Crowther Heidi K. Hillesland Katelyn R. Keyloun Molly C. Reid Maria Jose Lafuente-Monasterio Sonja Ghidelli-Disse Stephen E. Leonard Panqing He Jackson C. Jones Mallory M. Krahn Jack S. Mo Kartheek S. Dasari Anna M. W. Fox Markus Boesche Majida El Bakkouri Kasey L. Rivas Didier Leroy Raymond Hui Gerard Drewes Dustin J. Maly Wesley C. Van Voorhis Kayode K. Ojo 《PloS one》2016,11(3)
In 2010 the identities of thousands of anti-Plasmodium compounds were released publicly to facilitate malaria drug development. Understanding these compounds’ mechanisms of action—i.e., the specific molecular targets by which they kill the parasite—would further facilitate the drug development process. Given that kinases are promising anti-malaria targets, we screened ~14,000 cell-active compounds for activity against five different protein kinases. Collections of cell-active compounds from GlaxoSmithKline (the ~13,000-compound Tres Cantos Antimalarial Set, or TCAMS), St. Jude Children’s Research Hospital (260 compounds), and the Medicines for Malaria Venture (the 400-compound Malaria Box) were screened in biochemical assays of Plasmodium falciparum calcium-dependent protein kinases 1 and 4 (CDPK1 and CDPK4), mitogen-associated protein kinase 2 (MAPK2/MAP2), protein kinase 6 (PK6), and protein kinase 7 (PK7). Novel potent inhibitors (IC50 < 1 μM) were discovered for three of the kinases: CDPK1, CDPK4, and PK6. The PK6 inhibitors are the most potent yet discovered for this enzyme and deserve further scrutiny. Additionally, kinome-wide competition assays revealed a compound that inhibits CDPK4 with few effects on ~150 human kinases, and several related compounds that inhibit CDPK1 and CDPK4 yet have limited cytotoxicity to human (HepG2) cells. Our data suggest that inhibiting multiple Plasmodium kinase targets without harming human cells is challenging but feasible. 相似文献
4.
Hall Sawyer Mallory S. Lambert Jerod A. Merkle 《The Journal of wildlife management》2020,84(5):930-937
Fine-scale movement data has transformed our knowledge of ungulate migration ecology and now provides accurate, spatially explicit maps of migratory routes that can inform planning and management at local, state, and federal levels. Among the most challenging land use planning issues has been developing energy resources on public lands that overlap with important ungulate habitat, including the migratory routes of mule deer (Odocoileus hemionus). We generally know that less development is better for minimizing negative effects and maintaining habitat function, but we lack information on the amount of disturbance that animals can tolerate before reducing use of or abandoning migratory habitat. We used global positioning system data from 56 deer across 15 years to evaluate how surface disturbance from natural gas well pads and access roads in western Wyoming, USA, affected habitat selection of mule deer during migration and whether any disturbance threshold(s) existed beyond which use of migratory habitat declined. We used resource and step selection functions to examine disturbance thresholds at 3 different spatial scales. Overall, migratory use by mule deer declined as surface disturbance increased. Based on the weight of evidence from our 3 independent but complementary metrics, declines in migratory use related to surface disturbance were non-linear, where migratory use sharply declined when surface disturbance from energy development exceeded 3%. Disturbance thresholds may vary across regions, species, or migratory habitats (e.g., stopover sites). Such information can help with management and land use decisions related to mineral leasing and energy development that overlap with the migratory routes of ungulates. © 2020 The Wildlife Society. 相似文献
5.
William J. Joiner Eliot B. Friedman Hsiao-Tung Hung Kyunghee Koh Mallory Sowcik Amita Sehgal Max B. Kelz 《PLoS genetics》2013,9(9)
A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call neural inertia. Here we show that neural inertia is controlled by processes that contribute to sleep homeostasis and requires four genes involved in electrical excitability: Sh, sss, na and unc79. Although loss of function mutations in these genes can increase or decrease sensitivity to anesthesia induction, surprisingly, they all collapse neural inertia. These effects are genetically selective: neural inertia is not perturbed by loss-of-function mutations in all genes required for the sleep/wake cycle. These effects are also anatomically selective: sss acts in different neurons to influence arousal-promoting and arousal-suppressing processes underlying neural inertia. Supporting the idea that anesthesia and sleep share some, but not all, genetic and anatomical arousal-regulating pathways, we demonstrate that increasing homeostatic sleep drive widens the neural inertial barrier. We propose that processes selectively contributing to sleep homeostasis and neural inertia may be impaired in pathophysiological conditions such as coma and persistent vegetative states. 相似文献
6.
7.
Hayley L. Crowell Katherine C. King James M. Whelan Mallory V. Harmel Gennesee Garcia Sebastian G. Gonzales Paul H. Maier Heather Neldner Thomas Nhu John T. Nolan Emily N. Taylor 《Ecology and evolution》2021,11(12):8170
- Most studies on how rising temperatures will impact terrestrial ectotherms have focused on single populations or multiple sympatric species. Addressing the thermal and energetic implications of climatic variation on multiple allopatric populations of a species will help us better understand how a species may be impacted by altered climates.
- We used eight years of thermal and behavioral data collected from four populations of Pacific rattlesnakes (Crotalus oreganus) living in climatically distinct habitat types (inland and coastal) to determine the field‐active and laboratory‐preferred body temperatures, thermoregulatory metrics, and maintenance energetic requirements of snakes from each population.
- Physical models showed that thermal quality was best at coastal sites, but inland snakes thermoregulated more accurately despite being in more thermally constrained environments. Projected increases of 1 and 2°C in ambient temperature result in an increase in overall thermal quality at both coastal and inland sites.
- Population differences in modeled standard metabolic rate estimates were driven by body size and not field‐active body temperature, with inland snakes requiring 1.6× more food annually than coastal snakes.
- All snakes thermoregulated with high accuracy, suggesting that small increases in ambient temperature are unlikely to impact the maintenance energetic requirements of individual snakes and that some species of large‐bodied reptiles may be robust to modest thermal perturbations under conservative climate change predictions.
8.
Quan Zhang Mallory Barnes Michael Benson Elizabeth Burakowski A. Christopher Oishi Andrew Ouimette Rebecca Sanders‐DeMott Paul C. Stoy Matt Wenzel Lihua Xiong Koong Yi Kimberly A. Novick 《Global Change Biology》2020,26(6):3384-3401
Land‐use/cover change (LUCC) is an important driver of environmental change, occurring at the same time as, and often interacting with, global climate change. Reforestation and deforestation have been critical aspects of LUCC over the past two centuries and are widely studied for their potential to perturb the global carbon cycle. More recently, there has been keen interest in understanding the extent to which reforestation affects terrestrial energy cycling and thus surface temperature directly by altering surface physical properties (e.g., albedo and emissivity) and land–atmosphere energy exchange. The impacts of reforestation on land surface temperature and their mechanisms are relatively well understood in tropical and boreal climates, but the effects of reforestation on warming and/or cooling in temperate zones are less certain. This study is designed to elucidate the biophysical mechanisms that link land cover and surface temperature in temperate ecosystems. To achieve this goal, we used data from six paired eddy‐covariance towers over co‐located forests and grasslands in the temperate eastern United States, where radiation components, latent and sensible heat fluxes, and meteorological conditions were measured. The results show that, at the annual time scale, the surface of the forests is 1–2°C cooler than grasslands, indicating a substantial cooling effect of reforestation. The enhanced latent and sensible heat fluxes of forests have an average cooling effect of ?2.5°C, which offsets the net warming effect (+1.5°C) of albedo warming (+2.3°C) and emissivity cooling effect (?0.8°C) associated with surface properties. Additional daytime cooling over forests is driven by local feedbacks to incoming radiation. We further show that the forest cooling effect is most pronounced when land surface temperature is higher, often exceeding ?5°C. Our results contribute important observational evidence that reforestation in the temperate zone offers opportunities for local climate mitigation and adaptation. 相似文献
9.
Du Siqi Sung Yu-Sheng Wey Michael Wang Yadi Alatrash Nagham Berthod Alain MacDonnell Frederick M. Armstrong Daniel W. 《Molecular biology reports》2020,47(9):6749-6758
Molecular Biology Reports - N-methyl-d-aspartate (NMDA) receptors, which are widely present in the central nervous system, have also been found to be up-regulated in a variety of cancer cells and... 相似文献
10.
Grace?S?Tan Rebecca?Lewandowski Michael?J?Mallory Randy?Strich Katrina?F?CooperEmail author 《Cell division》2013,8(1):9