全文获取类型
收费全文 | 690篇 |
免费 | 67篇 |
出版年
2023年 | 14篇 |
2022年 | 20篇 |
2021年 | 46篇 |
2020年 | 19篇 |
2019年 | 23篇 |
2018年 | 24篇 |
2017年 | 22篇 |
2016年 | 30篇 |
2015年 | 61篇 |
2014年 | 54篇 |
2013年 | 47篇 |
2012年 | 71篇 |
2011年 | 50篇 |
2010年 | 27篇 |
2009年 | 31篇 |
2008年 | 28篇 |
2007年 | 28篇 |
2006年 | 24篇 |
2005年 | 12篇 |
2004年 | 19篇 |
2003年 | 18篇 |
2002年 | 16篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1992年 | 3篇 |
1980年 | 2篇 |
1976年 | 2篇 |
1968年 | 5篇 |
1967年 | 2篇 |
1957年 | 1篇 |
1955年 | 1篇 |
1954年 | 1篇 |
1949年 | 1篇 |
1948年 | 1篇 |
1939年 | 1篇 |
1936年 | 1篇 |
1934年 | 1篇 |
1933年 | 1篇 |
1932年 | 2篇 |
1929年 | 2篇 |
1928年 | 1篇 |
1926年 | 1篇 |
1924年 | 1篇 |
1922年 | 1篇 |
1911年 | 3篇 |
排序方式: 共有757条查询结果,搜索用时 218 毫秒
11.
Eichinger Jonas F. Grill Maximilian J. Kermani Iman Davoodi Aydin Roland C. Wall Wolfgang A. Humphrey Jay D. Cyron Christian J. 《Biomechanics and modeling in mechanobiology》2021,20(5):1851-1870
Biomechanics and Modeling in Mechanobiology - Living soft tissues appear to promote the development and maintenance of a preferred mechanical state within a defined tolerance around a so-called set... 相似文献
12.
Caio Cesar de Souza Alves Adam Collison Luke Hatchwell Maximilian Plank Matthew Morten Paul S. Foster Sebastian L. Johnston Cristiane Fran?a da Costa Mauro Vieira de Almeida Henrique Couto Teixeira Ana Paula Ferreira Joerg Mattes 《PloS one》2013,8(11)
Background
Severe asthma is associated with T helper (TH) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro.Objective
To determine the anti-inflammatory potential of anthraquinones in-vivo.Methods
BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation.Results
Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of TH2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung.Conclusion
Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT. 相似文献13.
In a recent study we investigated the complex mechanisms regulating the pollen release via thigmonastic stamen movement found exclusively in Loasaceae subfamily Loasoideae. We demonstrated that stamen movement is modulated by abiotic (light and temperature) as well as biotic stimuli (pollinator availability and visitation frequency). This is explained as a mechanism to adjust the rate of stamen movement and thus pollen dispensation to different environmental conditions in order to optimize pollen transfer. Stamen movement is rapid and thus a near-immediate response to pollinator visits. However, Loasaceae flowers also show a response to biotic stimuli on a longer time scale, by adjusting the duration of both the staminate and the carpellate phase of the anthesis. We here present two additional data sets on species not previously studied, underscoring the shortening of the staminate phase in the presence of pollinator visits vs. their absence and the shortening of the carpellate phase after pollination. Overall, the plant shows not only a rapid but an “intelligent” reaction to its environment in adjusting anthesis and pollen presentation to a range of factors. The physiological and morphological bases of the stamen movement are poorly understood. Our previous study showed that there is no direct spatial relationship between the place of stimulation in the flower and the stamen bundle activated. We here further show the morphological basis for stamen movement from a reflexed into an erect position: Only the basal part of the filament curves around the receptacle, while the upper part of the filament retains its shape. We hypothesize that the stimulus is transmitted over the entire receptacle and the place of reaction is determined by stamen maturity, not the location of the stimulus. 相似文献
14.
Maria Rohm Anke Sommerfeld Daniela Strzoda Allan Jones Tjeerd P. Sijmonsma Gottfried Rudofsky Christian Wolfrum Carsten Sticht Norbert Gretz Maximilian Zeyda Lukas Leitner Peter P. Nawroth Thomas M. Stulnig Mauricio Berriel Diaz Alexandros Vegiopoulos Stephan Herzig 《Cell metabolism》2013,17(4):575-585
- Download : Download high-res image (175KB)
- Download : Download full-size image
15.
16.
Dag Heinemann Markus Schomaker Stefan Kalies Maximilian Schieck Regina Carlson Hugo Murua Escobar Tammo Ripken Heiko Meyer Alexander Heisterkamp 《PloS one》2013,8(3)
Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types. 相似文献
17.
Javan M. Bauder Maximilian L. Allen Adam A. Ahlers Thomas J. Benson Craig A. Miller Kirk W. Stodola 《The Journal of wildlife management》2020,84(7):1234-1245
An accurate understanding of harvest trends is required for effective wildlife management. Trapper harvest data represent valuable long-term data for evaluating patterns and trends for wildlife species at broad spatiotemporal scales. Inferring accurate trends from harvest data, however, first requires identifying and controlling for confounding factors that vary independent of abundance. We investigated trends in 43 years of trapper harvest data (1976–2018) from Illinois, USA, for red fox (Vulpes vulpes), gray fox (Urocyon cinereoargenteus), and coyote (Canis latrans) while controlling for factors that may affect trapper effort, including number of effective (i.e., successful) trappers, pelt price, gasoline price, winter unemployment, and winter weather conditions. Annual trapper harvest for red and gray foxes declined and was affected by gasoline price and winter unemployment, whereas annual trapper harvest for coyotes increased and was not strongly affected by other covariates. After adjusting for pelt price, harvest of red foxes was relatively stable, but harvest of gray foxes declined and harvest of coyotes increased. Effects of covariates on harvest per successful trapper varied by species; nevertheless, we detected an increasing trend for coyotes and decreasing trends for gray foxes and red foxes. Concordance across indices for gray foxes and coyotes was consistent with hypothesized declines for gray foxes and increases for coyotes in the midwestern United States. Trends for red foxes varied depending on how we accounted for potential confounding factors and it is unclear if these trends suggest population declines or distribution shifts to urban areas with reduced trapping susceptibility. Our results highlight the importance of understanding sources of variation in harvest data and that their effects can vary across species. © 2020 The Wildlife Society. 相似文献
18.
Javan M. Bauder Kirk W. Stodola Thomas J. Benson Craig A. Miller Maximilian L. Allen 《The Journal of wildlife management》2020,84(8):1601-1610
Trapping data have a long and rich history of use in monitoring furbearer populations in North America but understanding the influences of variation in trapper harvest is important. Many factors besides abundance can cause variation in trapper harvest, including socioeconomics, weather, and motivation. The relationships between these extrinsic factors and trapper harvest may change temporally, which may obscure the causal understanding of variation in trapper harvest. We tested for changes in the relationships between pelt price and trapper numbers, and pelt price and harvest per trapper for raccoons (Procyon lotor) in Illinois, USA, from 1976–2018 while controlling for other socioeconomic (gasoline price, unemployment) and weather (temp, snow depth) factors. The annual raccoon harvest showed no clear trend, whereas the number of raccoon trappers declined markedly from approximately 1976–1990 in conjunction with pelt prices, after which the number of trappers remained relatively stable and were not significantly affected by pelt price. In contrast, harvest per trapper increased markedly during the 1990s and showed a significant negative relationship with pelt price pre-1990 but a positive relationship post-1990. We propose that declines in pelt prices resulted in a loss of less experienced or economically incentivized trappers, whereas contemporary trappers may continue trapping primarily for non-economic reasons. Our study highlights the potential for using non-linear relationships between trapper harvest data and socioeconomic covariates to help understand the influences of temporal variation in trapper harvest data. © 2020 The Wildlife Society. 相似文献
19.
Phillipp Kirfel Marisa Skaljac Jens Grotmann Tobias Kessel Maximilian Seip Katja Michaelis Andreas Vilcinskas 《Archives of insect biochemistry and physiology》2020,103(3):e21614
Histone acetylation is an evolutionarily conserved epigenetic mechanism of eukaryotic gene regulation which is tightly controlled by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In insects, life-history traits such as longevity and fecundity are severely affected by the suppression of HAT/HDAC activity, which can be achieved by RNA-mediated gene silencing or the application of chemical inhibitors. We used both experimental approaches to investigate the effect of HAT/HDAC inhibition in the pea aphid (Acyrthosiphon pisum) a model insect often used to study complex life-history traits. The silencing of HAT genes (kat6b, kat7, and kat14) promoted survival or increased the number of offspring, whereas targeting rpd3 (HDAC) reduced the number of viviparous offspring but increased the number of premature nymphs, suggesting a role in embryogenesis and eclosion. Specific chemical inhibitors of HATs/HDACs showed a remarkably severe impact on life-history traits, reducing survival, delaying development, and limiting the number of offspring. The selective inhibition of HATs and HDACs also had opposing effects on aphid body weight. The suppression of HAT/HDAC activity in aphids by RNA interference or chemical inhibition revealed similarities and differences compared to the reported role of these enzymes in other insects. Our data suggest that gene expression in A. pisum is regulated by multiple HATs/HDACs, as indicated by the fitness costs triggered by inhibitors that suppress several of these enzymes simultaneously. Targeting multiple HATs or HDACs with combined effects on gene regulation could, therefore, be a promising approach to discover novel targets for the management of aphid pests. 相似文献
20.
Dola Das Ehsan Fayazzadeh Xin Li Nischal Koirala Akshay Wadera Min Lang Maximilian Zernic Catherine Panick Pete Nesbitt Gordon McLennan 《Journal of cellular physiology》2020,235(9):6167-6182
Hepatocellular carcinoma (HCC) is a major health problem worldwide and in the United States as its incidence has increased substantially within the past two decades. HCC therapy remains a challenge, primarily due to underlying liver disorders such as cirrhosis that determines treatment approach and efficacy. Activated hepatic stellate cells (A-HSCs) are the key cell types involved in hepatic fibrosis/cirrhosis. A-HSCs are important constituents of HCC tumor microenvironment (TME) and support tumor growth, chemotherapy resistance, cancer cell migration, and escaping immune surveillance. This makes A-HSCs an important therapeutic target in hepatic fibrosis/cirrhosis as well as in HCC. Although many studies have reported the role of A-HSCs in cancer generation and investigated the therapeutic potential of A-HSCs reversion in cancer arrest, not much is known about inactivated or quiescent HSCs (Q-HSCs) in cancer growth or arrest. Here we report that Q-HSCs resist cancer cell growth by inducing cytotoxicity and enhancing chemotherapy sensitivity. We observed that the conditioned media from Q-HSCs (Q-HSCCM) induces cancer cell death through a caspase-independent mechanism that involves an increase in apoptosis-inducing factor expression, nuclear localization, DNA fragmentation, and cell death. We further observed that Q-HSCCM enhanced the efficiency of doxorubicin, as measured by cell viability assay. Exosomes present in the conditioned media were not involved in the mechanism, which suggests the role of other factors (proteins, metabolites, or microRNA) secreted by the cells. Identification and characterization of these factors are important in the development of effective HCC therapy. 相似文献