全文获取类型
收费全文 | 174篇 |
免费 | 1篇 |
专业分类
系统科学 | 4篇 |
教育与普及 | 1篇 |
理论与方法论 | 3篇 |
现状及发展 | 26篇 |
研究方法 | 29篇 |
综合类 | 111篇 |
自然研究 | 1篇 |
出版年
2022年 | 1篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 6篇 |
2015年 | 2篇 |
2014年 | 1篇 |
2013年 | 2篇 |
2012年 | 16篇 |
2011年 | 31篇 |
2010年 | 6篇 |
2009年 | 2篇 |
2008年 | 19篇 |
2007年 | 12篇 |
2006年 | 12篇 |
2005年 | 14篇 |
2004年 | 13篇 |
2003年 | 15篇 |
2002年 | 11篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
排序方式: 共有175条查询结果,搜索用时 15 毫秒
101.
Jürgen Schnekenburger Ina-Alexandra Weber Daniela Hahn Igor Buchwalow Burkhard Krüger Elke Albrecht Wolfram Domschke Markus M. Lerch 《Cellular and molecular life sciences : CMLS》2009,66(15):2525-2537
The regulated secretion of pancreatic zymogens depends on a functional cytoskeleton and intracellular vesicle transport. To
study the dynamics of tubulin and its motor proteins dynein and kinesin during secretion in pancreatic acinar cells, we infused
rats with 0.1 μg/kg/h caerulein. Electron and fluorescence microscopy detected neither dynein nor kinesin at the apical secretory
pole, nor on the surface of mature zymogen granules. After 30 min of secretagogue stimulation, kinesin and the Golgi marker
protein 58 K were reallocated towards the apical plasma membrane and association of kinesin with tubulin was enhanced. Disruption
of acinar cell microtubules had no effect on initial caerulein-induced amylase release but completely blocked secretion during
a second stimulus. Our results suggest that mature zymogen granule exocytosis is independent of intact microtubules, kinesin
and dynein. However, microtubule-dependent mechanisms seem to be important for the replenishment of secretory vesicles by
redistribution of Golgi elements towards the apical cell pole.
J. Schnekenburger and I.-A. Weber have contributed equally to this work. 相似文献
102.
RA Scott V Lagou RP Welch E Wheeler ME Montasser J Luan R Mägi RJ Strawbridge E Rehnberg S Gustafsson S Kanoni LJ Rasmussen-Torvik L Yengo C Lecoeur D Shungin S Sanna C Sidore PC Johnson JW Jukema T Johnson A Mahajan N Verweij G Thorleifsson JJ Hottenga S Shah AV Smith B Sennblad C Gieger P Salo M Perola NJ Timpson DM Evans BS Pourcain Y Wu JS Andrews J Hui LF Bielak W Zhao M Horikoshi P Navarro A Isaacs JR O'Connell K Stirrups V Vitart C Hayward T Esko E Mihailov RM Fraser T Fall BF Voight 《Nature genetics》2012,44(9):991-1005
Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control. 相似文献
103.
Pasternack SM von Kügelgen I Al Aboud K Lee YA Rüschendorf F Voss K Hillmer AM Molderings GJ Franz T Ramirez A Nürnberg P Nöthen MM Betz RC 《Nature genetics》2008,40(3):329-334
Hypotrichosis simplex is a group of nonsyndromic human alopecias. We mapped an autosomal recessive form of this disorder to chromosome 13q14.11-13q21.33, and identified homozygous truncating mutations in P2RY5, which encodes an orphan G protein-coupled receptor. Furthermore, we identified oleoyl-L-alpha-lysophosphatidic acid (LPA), a bioactive lipid, as a ligand for P2Y5 in reporter gene and radioligand binding experiments. Homology and studies of signaling transduction pathways suggest that P2Y5 is a member of a subgroup of LPA receptors, which also includes LPA4 and LPA5. Our study is the first to implicate a G protein-coupled receptor as essential for and specific to the maintenance of human hair growth. This finding may provide opportunities for new therapeutic approaches to the treatment of hair loss in humans. 相似文献
104.
Lisa Seipold Hermann Altmeppen Tomas Koudelka Andreas Tholey Petr Kasparek Radislav Sedlacek Michaela Schweizer Julia Bär Marina Mikhaylova Markus Glatzel Paul Saftig 《Cellular and molecular life sciences : CMLS》2018,75(17):3251-3267
A disintegrin and metalloproteinase 10 (ADAM10) plays a major role in the ectodomain shedding of important surface molecules with physiological and pathological relevance including the amyloid precursor protein (APP), the cellular prion protein, and different cadherins. Despite its therapeutic potential, there is still a considerable lack of knowledge how this protease is regulated. We have previously identified tetraspanin15 (Tspan15) as a member of the TspanC8 family to specifically associate with ADAM10. Cell-based overexpression experiments revealed that this binding affected the maturation process and surface expression of the protease. Our current study shows that Tspan15 is abundantly expressed in mouse brain, where it specifically interacts with endogenous ADAM10. Tspan15 knockout mice did not reveal an overt phenotype but showed a pronounced decrease of the active and mature form of ADAM10, an effect which augmented with aging. The decreased expression of active ADAM10 correlated with an age-dependent reduced shedding of neuronal (N)-cadherin and the cellular prion protein. APP α-secretase cleavage and the expression of Notch-dependent genes were not affected by the loss of Tspan15, which is consistent with the hypothesis that different TspanC8s cause ADAM10 to preferentially cleave particular substrates. Analyzing spine morphology revealed no obvious differences between Tspan15 knockout and wild-type mice. However, Tspan15 expression was elevated in brains of an Alzheimer’s disease mouse model and of patients, suggesting that upregulation of Tspan15 expression reflects a cellular response in a disease state. In conclusion, our data show that Tspan15 and most likely also other members of the TspanC8 family are central modulators of ADAM10-mediated ectodomain shedding in vivo. 相似文献
105.
Evidence for complete denitrification in a benthic foraminifer 总被引:2,自引:0,他引:2
Risgaard-Petersen N Langezaal AM Ingvardsen S Schmid MC Jetten MS Op den Camp HJ Derksen JW Piña-Ochoa E Eriksson SP Nielsen LP Revsbech NP Cedhagen T van der Zwaan GJ 《Nature》2006,443(7107):93-96
Benthic foraminifera are unicellular eukaryotes found abundantly in many types of marine sediments. Many species survive and possibly reproduce in anoxic habitats, but sustainable anaerobic metabolism has not been previously described. Here we demonstrate that the foraminifer Globobulimina pseudospinescens accumulates intracellular nitrate stores and that these can be respired to dinitrogen gas. The amounts of nitrate detected are estimated to be sufficient to support respiration for over a month. In a Swedish fjord sediment where G. pseudospinescens is the dominant foraminifer, the intracellular nitrate pool in this species accounted for 20% of the large, cell-bound, nitrate pool present in an oxygen-free zone. Similarly high nitrate concentrations were also detected in foraminifera Nonionella cf. stella and a Stainforthia species, the two dominant benthic taxa occurring within the oxygen minimum zone of the continental shelf off Chile. Given the high abundance of foraminifera in anoxic marine environments, these new findings suggest that foraminifera may play an important role in global nitrogen cycling and indicate that our understanding of the complexity of the marine nitrogen cycle is far from complete. 相似文献
106.
Deciphering the evolution and metabolism of an anammox bacterium from a community genome 总被引:15,自引:0,他引:15
Strous M Pelletier E Mangenot S Rattei T Lehner A Taylor MW Horn M Daims H Bartol-Mavel D Wincker P Barbe V Fonknechten N Vallenet D Segurens B Schenowitz-Truong C Médigue C Collingro A Snel B Dutilh BE Op den Camp HJ van der Drift C Cirpus I van de Pas-Schoonen KT Harhangi HR van Niftrik L Schmid M Keltjens J van de Vossenberg J Kartal B Meier H Frishman D Huynen MA Mewes HW Weissenbach J Jetten MS Wagner M Le Paslier D 《Nature》2006,440(7085):790-794
Anaerobic ammonium oxidation (anammox) has become a main focus in oceanography and wastewater treatment. It is also the nitrogen cycle's major remaining biochemical enigma. Among its features, the occurrence of hydrazine as a free intermediate of catabolism, the biosynthesis of ladderane lipids and the role of cytoplasm differentiation are unique in biology. Here we use environmental genomics--the reconstruction of genomic data directly from the environment--to assemble the genome of the uncultured anammox bacterium Kuenenia stuttgartiensis from a complex bioreactor community. The genome data illuminate the evolutionary history of the Planctomycetes and allow us to expose the genetic blueprint of the organism's special properties. Most significantly, we identified candidate genes responsible for ladderane biosynthesis and biological hydrazine metabolism, and discovered unexpected metabolic versatility. 相似文献
107.
108.
Natural materials are renowned for exquisite designs that optimize function, as illustrated by the elasticity of blood vessels, the toughness of bone and the protection offered by nacre. Particularly intriguing are spider silks, with studies having explored properties ranging from their protein sequence to the geometry of a web. This material system, highly adapted to meet a spider's many needs, has superior mechanical properties. In spite of much research into the molecular design underpinning the outstanding performance of silk fibres, and into the mechanical characteristics of web-like structures, it remains unknown how the mechanical characteristics of spider silk contribute to the integrity and performance of a spider web. Here we report web deformation experiments and simulations that identify the nonlinear response of silk threads to stress--involving softening at a yield point and substantial stiffening at large strain until failure--as being crucial to localize load-induced deformation and resulting in mechanically robust spider webs. Control simulations confirmed that a nonlinear stress response results in superior resistance to structural defects in the web compared to linear elastic or elastic-plastic (softening) material behaviour. We also show that under distributed loads, such as those exerted by wind, the stiff behaviour of silk under small deformation, before the yield point, is essential in maintaining the web's structural integrity. The superior performance of silk in webs is therefore not due merely to its exceptional ultimate strength and strain, but arises from the nonlinear response of silk threads to strain and their geometrical arrangement in a web. 相似文献
109.
Eva C. Schwarz Christina Backes Arne Knörck Nicole Ludwig Petra Leidinger Cora Hoxha Gertrud Schwär Thomas Grossmann Sabine C. Müller Martin Hart Jan Haas Valentina Galata Isabelle Müller Tobias Fehlmann Hermann Eichler Andre Franke Benjamin Meder Eckart Meese Markus Hoth Andreas Keller 《Cellular and molecular life sciences : CMLS》2016,73(16):3169-3181
110.