全文获取类型
收费全文 | 1525篇 |
免费 | 121篇 |
国内免费 | 1篇 |
出版年
2024年 | 2篇 |
2023年 | 17篇 |
2022年 | 33篇 |
2021年 | 61篇 |
2020年 | 43篇 |
2019年 | 42篇 |
2018年 | 29篇 |
2017年 | 37篇 |
2016年 | 65篇 |
2015年 | 124篇 |
2014年 | 105篇 |
2013年 | 120篇 |
2012年 | 183篇 |
2011年 | 134篇 |
2010年 | 96篇 |
2009年 | 65篇 |
2008年 | 84篇 |
2007年 | 103篇 |
2006年 | 73篇 |
2005年 | 63篇 |
2004年 | 40篇 |
2003年 | 36篇 |
2002年 | 24篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1966年 | 2篇 |
1963年 | 1篇 |
排序方式: 共有1647条查询结果,搜索用时 15 毫秒
11.
12.
Penelope A. Ajani Hong Chang Lim Arjun Verma Malwenn Lassudrie Katie McBean Martina A. Doblin Shauna A. Murray 《Phycological Research》2020,68(3):254-259
Certain species of the marine diatom genus Pseudo‐nitzschia are responsible for the production of the domoic acid (DA), a neurotoxin that can bioaccumulate in the food chain and cause amnesic shellfish poisoning (ASP) in animals and humans. This study extends our knowledge by reporting on the first observation of the potentially toxic species Pseudo‐nitzschia simulans from this region. One clonal strain of P. simulans was isolated from the East Australian Current and characterized using light and transmission electron microscopy, and phylogenetic analyses based on regions of the internal transcribed spacer (ITS) and the D1–D3 region of the large subunit (LSU) of the nuclear‐encoded ribosomal deoxyribonucleic acid (rDNA), as well as examined for DA production as measured by liquid chromatography–mass spectrometry. Although this strain was non‐toxic under the defined growth conditions, the results unambiguously confirmed that this isolate is the potentially toxic species P. simulans – the first report of this species from the Southern Hemisphere. 相似文献
13.
The importance of DNA methylation in mammalian and plant systems is well established. In recent years there has been renewed interest in DNA methylation in insects. Accumulating evidence, both from mammals and insects, points towards an emerging role for DNA methylation in the regulation of phenotypic plasticity. The migratory locust (Locusta migratoria) is a model organism for the study of phenotypic plasticity. Despite this, there is little information available about the degree to which the genome is methylated in this species and genes encoding methylation machinery have not been previously identified. We therefore undertook an initial investigation to establish the presence of a functional DNA methylation system in L. migratoria. We found that the migratory locust possesses genes that putatively encode methylation machinery (DNA methyltransferases and a methyl-binding domain protein) and exhibits genomic methylation, some of which appears to be localised to repetitive regions of the genome. We have also identified a distinct group of genes within the L. migratoria genome that appear to have been historically methylated and show some possible functional differentiation. These results will facilitate more detailed research into the functional significance of DNA methylation in locusts. 相似文献
14.
15.
RueiLung Lin Hilaree N. Frazier Katie L. Anderson Sami L. Case Adam O. Ghoweri Olivier Thibault 《Aging cell》2022,21(7)
Neuronal hippocampal Ca2+ dysregulation is a critical component of cognitive decline in brain aging and Alzheimer''s disease and is suggested to impact communication and excitability through the activation of a larger after hyperpolarization. However, few studies have tested for the presence of Ca2+ dysregulation in vivo, how it manifests, and whether it impacts network function across hundreds of neurons. Here, we tested for neuronal Ca2+ network dysregulation in vivo in the primary somatosensory cortex (S1) of anesthetized young and aged male Fisher 344 rats using single‐cell resolution techniques. Because S1 is involved in sensory discrimination and proprioception, we tested for alterations in ambulatory performance in the aged animal and investigated two potential pathways underlying these central aging‐ and Ca2+‐dependent changes. Compared to young, aged animals displayed increased overall activity and connectivity of the network as well as decreased ambulatory speed. In aged animals, intranasal insulin (INI) increased network synchronicity and ambulatory speed. Importantly, in young animals, delivery of the L‐type voltage‐gated Ca2+ channel modifier Bay‐K 8644 altered network properties, replicating some of the changes seen in the older animal. These results suggest that hippocampal Ca2+ dysregulation may be generalizable to other areas, such as S1, and might engage modalities that are associated with locomotor stability and motivation to ambulate. Further, given the safety profile of INI in the clinic and the evidence presented here showing that this central dysregulation is sensitive to insulin, we suggest that these processes can be targeted to potentially increase motivation and coordination while also reducing fall frequency with age. 相似文献
16.
Copper, an essential trace element acquired through nutrition, is an important co-factor for pro-angiogenic factors including vascular endothelial growth factor (VEGF). Decreasing bioavailable copper has been used as an anti-angiogenic and anti-cancer strategy with promising results. However, the role of copper and its potential as a therapy in mesothelioma is not yet well understood. Therefore, we monitored copper levels in progressing murine mesothelioma tumors and analyzed the effects of lowering bioavailable copper. Copper levels in tumors and organs were assayed using atomic absorption spectrophotometry. Mesothelioma tumors rapidly sequestered copper at early stages of development, the copper was then dispersed throughout growing tumor tissues. These data imply that copper uptake may play an important role in early tumor development. Lowering bioavailable copper using the copper chelators, penicillamine, trientine or tetrathiomolybdate, slowed in vivo mesothelioma growth but did not provide any cures similar to using cisplatin chemotherapy or anti-VEGF receptor antibody therapy. The impact of copper lowering on tumor blood vessels and tumor infiltrating T cells was measured using flow cytometry and confocal microscopy. Copper lowering was associated with reduced tumor vessel diameter, reduced endothelial cell proliferation (reduced Ki67 expression) and lower surface ICAM/CD54 expression implying reduced endothelial cell activation, in a process similar to endothelial normalization. Copper lowering was also associated with a CD4+ T cell infiltrate. In conclusion, these data suggest copper lowering is a potentially useful anti-mesothelioma treatment strategy that slows tumor growth to provide a window of opportunity for inclusion of other treatment modalities to improve patient outcomes. 相似文献
17.
18.
Albert L. Harting Michelle M. Barbieri Jason D. Baker Tracy A. Mercer Thea C. Johanos Stacie J. Robinson Charles L. Littnan Katie M. Colegrove Dave S. Rotstein 《Marine Mammal Science》2021,37(1):235-250
Identifying, assessing, and ranking the impact of individual threats is fundamental to the conservation and recovery of rare and endangered species. In this analysis, we quantify not only the frequency of specific causes-of-death (CODs) among Main Hawaiian Island (MHI) monk seals, but also assess the impact of individual CODs on the intrinsic growth rate, λ, of the MHI population. We used gross necropsy results, histopathology, and other evidence to assign probabilities of 11 COD types to each mortality and then used Monte Carlo sampling to evaluate the influence of each COD on λ. By right censoring realizations involving specific CODs, we were able to estimate λ (and its associated uncertainty) when CODs were selectively removed from influencing survival. Applying the analysis to all known and inferred deaths believed to have occurred 2004–2019, the CODs with the largest influence on λ were anthropogenic trauma, anthropogenic drowning, and protozoal disease. In aggregate, anthropogenic CODs had a larger effect on the growth rate than either natural or disease CODs. Possible bias associated with differential carcass detection, recovery, and COD classification are discussed. 相似文献
19.
20.
Katie J. Wolfe Hong Yu Ren Philipp Trepte Douglas M. Cyr 《Molecular biology of the cell》2013,24(23):3588-3602
Conformational diseases are associated with the conversion of normal proteins into aggregation-prone toxic conformers with structures similar to that of β-amyloid. Spatial distribution of amyloid-like proteins into intracellular quality control centers can be beneficial, but cellular mechanisms for protective aggregation remain unclear. We used a high-copy suppressor screen in yeast to identify roles for the Hsp70 system in spatial organization of toxic polyglutamine-expanded Huntingtin (Huntingtin with 103Q glutamine stretch [Htt103Q]) into benign assemblies. Under toxic conditions, Htt103Q accumulates in unassembled states and speckled cytosolic foci. Subtle modulation of Sti1 activity reciprocally affects Htt toxicity and the packaging of Htt103Q into foci. Loss of Sti1 exacerbates Htt toxicity and hinders foci formation, whereas elevation of Sti1 suppresses Htt toxicity while organizing small Htt103Q foci into larger assemblies. Sti1 also suppresses cytotoxicity of the glutamine-rich yeast prion [RNQ+] while reorganizing speckled Rnq1–monomeric red fluorescent protein into distinct foci. Sti1-inducible foci are perinuclear and contain proteins that are bound by the amyloid indicator dye thioflavin-T. Sti1 is an Hsp70 cochaperone that regulates the spatial organization of amyloid-like proteins in the cytosol and thereby buffers proteotoxicity caused by amyloid-like proteins. 相似文献