全文获取类型
收费全文 | 691篇 |
免费 | 50篇 |
国内免费 | 2篇 |
出版年
2023年 | 5篇 |
2022年 | 7篇 |
2021年 | 16篇 |
2020年 | 17篇 |
2019年 | 10篇 |
2018年 | 13篇 |
2017年 | 8篇 |
2016年 | 18篇 |
2015年 | 57篇 |
2014年 | 49篇 |
2013年 | 57篇 |
2012年 | 62篇 |
2011年 | 58篇 |
2010年 | 43篇 |
2009年 | 36篇 |
2008年 | 45篇 |
2007年 | 39篇 |
2006年 | 31篇 |
2005年 | 38篇 |
2004年 | 22篇 |
2003年 | 20篇 |
2002年 | 24篇 |
2001年 | 4篇 |
2000年 | 9篇 |
1999年 | 7篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 4篇 |
1975年 | 2篇 |
1972年 | 1篇 |
1969年 | 2篇 |
排序方式: 共有743条查询结果,搜索用时 31 毫秒
151.
Irina Vetter Filip Touska Andreas Hess Rachel Hinsbey Simon Sattler Angelika Lampert Marina Sergejeva Anastasia Sharov Lindon S Collins Mirjam Eberhardt Matthias Engel Peter J Cabot John N Wood Viktorie Vlachová Peter W Reeh Richard J Lewis Katharina Zimmermann 《The EMBO journal》2012,31(19):3795-3808
Ciguatoxins are sodium channel activator toxins that cause ciguatera, the most common form of ichthyosarcotoxism, which presents with peripheral sensory disturbances, including the pathognomonic symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling. We show that intraplantar injection of P-CTX-1 elicits cold allodynia in mice by targeting specific unmyelinated and myelinated primary sensory neurons. These include both tetrodotoxin-resistant, TRPA1-expressing peptidergic C-fibres and tetrodotoxin-sensitive A-fibres. P-CTX-1 does not directly open heterologously expressed TRPA1, but when co-expressed with Nav channels, sodium channel activation by P-CTX-1 is sufficient to drive TRPA1-dependent calcium influx that is responsible for the development of cold allodynia, as evidenced by a large reduction of excitatory effect of P-CTX-1 on TRPA1-deficient nociceptive C-fibres and of ciguatoxin-induced cold allodynia in TRPA1-null mutant mice. Functional MRI studies revealed that ciguatoxin-induced cold allodynia enhanced the BOLD (Blood Oxygenation Level Dependent) signal, an effect that was blunted in TRPA1-deficient mice, confirming an important role for TRPA1 in the pathogenesis of cold allodynia. 相似文献
152.
Mirjam Kn?rnschild Kirsten Jung Martina Nagy Markus Metz Elisabeth Kalko 《Proceedings. Biological sciences / The Royal Society》2012,279(1748):4827-4835
Bat echolocation is primarily used for orientation and foraging but also holds great potential for social communication. The communicative function of echolocation calls is still largely unstudied, especially in the wild. Eavesdropping on vocal signatures encoding social information in echolocation calls has not, to our knowledge, been studied in free-living bats so far. We analysed echolocation calls of the polygynous bat Saccopteryx bilineata and found pronounced vocal signatures encoding sex and individual identity. We showed experimentally that free-living males discriminate approaching male and female conspecifics solely based on their echolocation calls. Males always produced aggressive vocalizations when hearing male echolocation calls and courtship vocalizations when hearing female echolocation calls; hence, they responded with complex social vocalizations in the appropriate social context. Our study demonstrates that social information encoded in bat echolocation calls plays a crucial and hitherto underestimated role for eavesdropping conspecifics and thus facilitates social communication in a highly mobile nocturnal mammal. 相似文献
153.
Niewisch MR Ku?i Z Wolburg H Sautter M Krampen L Deubzer B Handgretinger R Bruchelt G 《Cellular physiology and biochemistry》2012,29(3-4):373-380
Many cancer cells metabolize glucose preferentially via pyruvate to lactate instead to CO(2) and H(2)O (oxidative phosphorylation) even in the presence of oxygen (Warburg effect). Dichloroacetate (DCA) is a drug which is able to shift pyruvate metabolism from lactate to acetyl-CoA (tricarboxylic acid cycle) by indirect activation of pyruvate dehydrogenase (PDH). This can subsequently lead to an increased flow of oxygen in the respiratory chain, associated with enhanced generation of reactive oxygen species (ROS) which may cause apoptosis. In order to investigate if DCA may be suitable for neuroblastoma therapy, it was investigated on three human neuroblastoma cell lines whether DCA can reduce lactate production and enhance oxygen consumption. The data show, that DCA (in the low millimolar range) is able to reduce lactate production, but there was only a slight shift to increased oxygen consumption and almost no effect on cell vitality, proliferation and apoptosis of the three cell lines investigated. Therefore, DCA at low millimolar concentrations seems to be only of minor efficacy for neuroblastoma treatment. 相似文献
154.
Flow cytometric investigations show binding of an isolated arabinogalactan-protein (AGP) from pressed juice of the aerial parts of Echinacea purpurea to the cell surface of human leucocytes. AGP demonstrates binding to lymphocytes, monocytes and granulocytes of different donors (n=8). Competition assays with two antibodies, directed against CD4 and CD8, revealed no interaction of AGP with these receptors, leading to the conclusion that binding of AGP to leucocytes is mediated via other structures. 相似文献
155.
Fleur S. van Dijk Eline H. Zwikstra Sander R. Piersma Connie R. Jimenez Alice C. Morsman Mirjam H.H. van Roij Jonathan I.M.L. Verbeke Nick J. Shaw Carole McKeown Ann Dalton Gerard Pals 《American journal of human genetics》2009,85(4):521-527
Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the α1 chains of collagen type I. This 3-prolyl hydroxylation is decreased in patients with CRTAP and P3H1 deficiency. It was suspected that mutations in the PPIB gene encoding CyPB would also cause OI with decreased collagen 3-prolyl hydroxylation. To our knowledge we present the first two families with recessive OI caused by PPIB gene mutations. The clinical phenotype is compatible with OI Sillence type II-B/III as seen with COL1A1/2, CRTAP, and LEPRE1 mutations. The percentage of 3-hydroxylated P986 residues in patients with PPIB mutations is decreased in comparison to normal, but it is higher than in patients with CRTAP and LEPRE1 mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the α1 chains of collagen type I. 相似文献
156.
To explore the feasability of larch (Larix decidua Mill.) embryogenic cell culture as alternative plant expression system, protein stability in fresh and conditioned medium
was characterized in this study and compared to tobacco BY2 suspension culture. Fresh and conditioned media were spiked with
1 μg human IgG and IgG content was determined by ELISA after 24 h incubation. In fresh media, IgG recovery rate decreased
to 12–23%. Adsorption on vessel walls probably is the best explanation for this IgG loss and EDTA in the medium strongly influenced
wall adsorption. A high IgG recovery rate occurred in all conditioned cell culture media (7 or 14 days after inoculation).
Changes in the low molecular weight-constitution of conditioned medium, rather than co-secreted polymers, are responsible
for IgG stability in the cell suspension cultures. 相似文献
157.
Engel E. Cayenne; Weltzin Jake F.; Norby Richard J.; Classen Aimee T. 《Journal of Plant Ecology》2009,2(1):1-11
Aims: The direct effects of atmospheric and climatic change factors—atmospheric[CO2], air temperature and changes in precipitation—canshape plant community composition and alter ecosystem function.It is essential to understand how these factors interact tomake better predictions about how ecosystems may respond tochange. We investigated the direct and interactive effects of[CO2], warming and altered soil moisture in open-top chambers(OTCs) enclosing a constructed old-field community to test howthese factors shape plant communities. Materials and methods: The experimental facility in Oak Ridge, TN, USA, made use of4-m diameter OTCs and rain shelters to manipulate [CO2] (ambient,ambient + 300 ppm), air temperature (ambient, ambient + 3.5°C)and soil moisture (wet, dry). The plant communities within thechambers comprised seven common old-field species, includinggrasses, forbs and legumes. We tracked foliar cover for eachspecies and calculated community richness, evenness and diversityfrom 2003 to 2005. Important findings: This work resulted in three main findings: (1) warming had species-specificeffects on foliar cover that varied through time and were alteredby soil moisture treatments; (2) [CO2] had little effect onindividual species or the community; (3) diversity, evennessand richness were influenced most by soil moisture, primarilyreflecting the response of one dominant species. We concludethat individualistic species responses to atmospheric and climaticchange can alter community composition and that plant populationsand communities should be considered as part of analyses ofterrestrial ecosystem response to climate change. However, predictionof plant community responses may be difficult given interactionsbetween factors and changes in response through time. 相似文献
158.
Elisabeth Frank Melanie S. Kessler Michaela D. Filiou Yaoyang Zhang Giuseppina Maccarrone Stefan Reckow Mirjam Bunck Hermann Heumann Christoph W. Turck Rainer Landgraf Boris Hambsch 《PloS one》2009,4(11)
The identification of differentially regulated proteins in animal models of psychiatric diseases is essential for a comprehensive analysis of associated psychopathological processes. Mass spectrometry is the most relevant method for analyzing differences in protein expression of tissue and body fluid proteomes. However, standardization of sample handling and sample-to-sample variability are problematic. Stable isotope metabolic labeling of a proteome represents the gold standard for quantitative mass spectrometry analysis. The simultaneous processing of a mixture of labeled and unlabeled samples allows a sensitive and accurate comparative analysis between the respective proteomes. Here, we describe a cost-effective feeding protocol based on a newly developed 15N bacteria diet based on Ralstonia eutropha protein, which was applied to a mouse model for trait anxiety. Tissue from 15N-labeled vs. 14N-unlabeled mice was examined by mass spectrometry and differences in the expression of glyoxalase-1 (GLO1) and histidine triad nucleotide binding protein 2 (Hint2) proteins were correlated with the animals'' psychopathological behaviors for methodological validation and proof of concept, respectively. Additionally, phenotyping unraveled an antidepressant-like effect of the incorporation of the stable isotope 15N into the proteome of highly anxious mice. This novel phenomenon is of considerable relevance to the metabolic labeling method and could provide an opportunity for the discovery of candidate proteins involved in depression-like behavior. The newly developed 15N bacteria diet provides researchers a novel tool to discover disease-relevant protein expression differences in mouse models using quantitative mass spectrometry. 相似文献
159.
Mirjam Kaestli Mark Mayo Glenda Harrington Linda Ward Felicity Watt Jason V. Hill Allen C. Cheng Bart J. Currie 《PLoS neglected tropical diseases》2009,3(1)