全文获取类型
收费全文 | 207篇 |
免费 | 20篇 |
出版年
2022年 | 3篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 5篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 5篇 |
2014年 | 12篇 |
2013年 | 20篇 |
2012年 | 21篇 |
2011年 | 9篇 |
2010年 | 11篇 |
2009年 | 3篇 |
2008年 | 13篇 |
2007年 | 13篇 |
2006年 | 7篇 |
2005年 | 6篇 |
2004年 | 9篇 |
2003年 | 10篇 |
2002年 | 4篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1994年 | 3篇 |
1993年 | 7篇 |
1992年 | 2篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1982年 | 2篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1975年 | 3篇 |
1973年 | 5篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1967年 | 1篇 |
1960年 | 1篇 |
1947年 | 1篇 |
1921年 | 1篇 |
1920年 | 1篇 |
1904年 | 1篇 |
排序方式: 共有227条查询结果,搜索用时 171 毫秒
61.
The type II and type III collagen α-1 chain N-telopeptides are a nonadecamer with the sequence pEMAGGFDEKAGGAQLGVMQ-NH2 and a tetradecamer with the sequence pEYEAYDVKSGVAGG-NH2, respectively. Their conformations have been studied in CD3OH/H2O (60/40) solution by means of two-dimensional proton nmr spectroscopy. Based on double quantum filtered correlation spectroscopy, total correlation spectroscopy, rotating frame nuclear Overhauser enhancement (ROE) spectroscopy, and nuclear Over-hauser enhancement (NOE) spectroscopy experiments, all resonances were assigned and the conformational properties were analyzed in terms of vicinal NH-Hα coupling constants, sequential and medium-range NOEs (ROEs), and amide proton temperature coefficients. The NOE distance constraints as well as dihedral constraints based on the vicinal NH-Hα coupling constants were used as input parameters for restrained molecular mechanics, consisting of restrained molecular dynamics and restrained energy minimization calculations. The type II N-telopeptide's conformation is dominated by a fused βγ-turn between Phe6 and Ala10, stabilized by three hydrogen bonds and a salt bridge between the side-chain end groups of Glu8 and Lys9. The first 5 amino acids are extended with a much higher degree of conformational freedom. The 2 Gly residues following the turns were found to be highly flexible (hinge-like), leaving the spatial position of the second half of the molecule relative to the fused βγ-turn undefined. In the type III telopeptide, a series of sequential NH(i)-NH(i + 1) ROEs were observed between the amino acids Tyr2 and Ser9, indicating that a fraction of the conformational space is helical. However, the absence of medium-range ROEs and the lack of regularity of the effects associated with α-helices suggest the presence of a nascent rather than a complete helix. © 1993 John Wiley & Sons, Inc. 相似文献
62.
Julie M. Jones Roger L. Albin Eva L. Feldman Karl Simin Timothy G. Schuster Wesley A. Dunnick John T. Collins C. E. Chrisp Benjamin A. Taylor Miriam H. Meisler 《Genomics》1993,16(3)
The autosomal recessive mutation mnd2 results in early onset motor neuron disease with rapidly progressive paralysis, severe muscle wasting, regression of thymus and spleen, and death before 40 days of age. mnd2 has been mapped to mouse chromosome 6 with the gene order: centromere-Tcrb-Ly-2-Sftp-3-D6Mit4-mnd2-D6Mit6, D6Mit9-D6Rck132-Raf-1, D6Mit11-D6Mit12-D6Mit14. mnd2 is located within a conserved linkage group with homologs on human chromosome 2p12-p13. Spinal motor neurons of homozygous affected animals are swollen and stain weakly, and electromyography revealed spontaneous activity characteristic of muscle denervation. Myelin staining was normal throughout the neuraxis. The clinical observations are consistent with a primary abnormality of lower motor neuron function. This new animal model will be of value for identification of a genetic defect responsible for motor neuron disease and for evaluation of new therapies. 相似文献
63.
Gerhild Zandonella Lutz Haalck Fritz Spener K. Faber Fritz Paltauf Albin Hermetter 《Chirality》1996,8(7):481-489
A new type of fluorogenic alkyldiacyl glycerols was synthesized and used as fluorogenic substrates for the analysis of lipase activities and stereoselectivities. These compounds contain perylene as a fluorophore and the trinitrophenylamino (TNP) residue as a quencher. Both substituents are covalently bound to the ω-ends of the sn-2 and sn-1(3) acyl chains, respectively. Upon glycerolipid hydrolysis, the residues are separated from each other thus allowing determination of lipase activity by the continuous increase in fluorescence intensity which is caused by dequenching. Using enantiomeric pairs of these compounds, we were able to analyze lipase stereoselectivity depending on the reaction medium. Mixtures of enantiomeric fluorogenic alkyldiacyl glycerols, selectively labelled with pyrene or perylene as fluorophores, can be used for a dual-wavelength “stereoassay” of lipases. Since absorption and emission maxima of both labels are clearly separated, hydrolysis of the respective enantiomeric substrates can be determined simultaneously, and the difference in the rates of hydrolysis can be taken as a parameter for the stereopreference of a lipase. Hydrolysis rates measured with perylene-substituted lipids are generally lower than those obtained with the pyrene analogs. Thus, with a mixture of perylene and pyrene-substituted lipids, we observe a higher apparent stereoselectivity of lipases since we measure a combination of stereo- and substrate selectivity. In the presence of albumin, all microbial lipases tested so far exhibit stereopreference for the sn-1 glycerol position. In our assay, the apparent stereoselectivities are highest if in the presence of albumin, the sn-1 position carries pyrene and the sn-3 position is substituted with perylene. The lipase stereoselectivity assay described here requires the simultaneous measurement of the fluorescence intensities at two different wavelengths in a single cuvette and can thus be carried out using existing and cheap instrumentation that was developed for the fluorimetric analysis of Ca++ concentrations. © 1996 Wiley-Liss, Inc. 相似文献
64.
65.
Christoph Nusshold Andreas Uellen Eva Bernhart Astrid Hammer Sabine Damm Andrea Wintersperger Helga Reicher Albin Hermetter Ernst Malle Wolfgang Sattler 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(12):1665-1678
Neuronal sphingolipids (SL) play important roles during axonal extension, neurotrophic receptor signaling and neurotransmitter release. Many of these signaling pathways depend on the presence of specialized membrane microdomains termed lipid rafts. Sphingomyelin (SM), one of the main raft constituents, can be formed de novo or supplied from exogenous sources. The present study aimed to characterize fluorescently-labeled SL turnover in a murine neuronal cell line (CATH.a). Our results demonstrate that at 4 °C exogenously added BODIPY-SM accumulates exclusively at the plasma membrane. Treatment of cells with bacterial sphingomyelinase (SMase) and back-exchange experiments revealed that 55–67% of BODIPY-SM resides in the outer leaflet of the plasma membrane. Endocytosis of BODIPY-SM occurs via caveolae with part of internalized BODIPY-fluorescence ending up in the Golgi and the ER. Following endocytosis BODIPY-SM undergoes hydrolysis, a reaction substantially faster than BODIPY-SM synthesis from BODIPY-ceramide. RNAi demonstrated that both, acid (a)SMase and neutral (n)SMases contribute to BODIPY-SM hydrolysis. Finally, high-density lipoprotein (HDL)-associated BODIPY-SM was efficiently taken up by CATH.a cells. Our findings indicate that endocytosis of exogenous SM occurs almost exclusively via caveolin-dependent pathways, that both, a- and nSMases equally contribute to neuronal SM turnover and that HDL-like particles might represent physiological SM carriers/donors in the brain. 相似文献
66.
Werner ER Hermetter A Prast H Golderer G Werner-Felmayer G 《Journal of lipid research》2007,48(6):1422-1427
An assay was set up for glyceryl ether monooxygenase activity in tissue samples using the novel substrate 1-O-pyrenedecyl-sn-glycerol and high-performance liquid chromatographic analysis of reaction mixtures with fluorescence detection, allowing robust detection of enzymatic activity in microgram amounts of tissue homogenates. The activity partially purified from rat liver strictly depended on the presence of a tetrahydropteridine. Tetrahydrobiopterin-dependent glyceryl ether monooxygenase activity was observed in all rat tissues tested except female heart, with highest activities in liver, intestine, and cerebellum. Activity was not uniformly distributed in brain: it was higher in cerebellum than in striatum or cortex. These data demonstrate that tetrahydrobiopterin-dependent glyceryl ether monooxygenase is found not only in liver and the gastrointestinal tract but also in brain and other organs of the rat and provide an additional goal for tetrahydrobiopterin biosynthesis in these organs. 相似文献
67.
Allison M. Land Nadine M. Shaban Leah Evans Judd F. Hultquist John S. Albin Reuben S. Harris 《Journal of virology》2014,88(21):12923-12927
HIV-1 Vif counteracts restrictive APOBEC3 proteins by targeting them for proteasomal degradation. To determine the regions mediating sensitivity to Vif, we compared human APOBEC3F, which is HIV-1 Vif sensitive, with rhesus APOBEC3F, which is HIV-1 Vif resistant. Rhesus-human APOBEC3F chimeras and amino acid substitution mutants were tested for sensitivity to HIV-1 Vif. This approach identified the α3 and α4 helices of human APOBEC3F as important determinants of the interaction with HIV-1 Vif. 相似文献
68.
69.
Karima Zouache Albin Fontaine Anubis Vega-Rua Laurence Mousson Jean-Michel Thiberge Ricardo Lourenco-De-Oliveira Valérie Caro Louis Lambrechts Anna-Bella Failloux 《Proceedings. Biological sciences / The Royal Society》2014,281(1792)
Interactions between pathogens and their insect vectors in nature are under the control of both genetic and non-genetic factors, yet most studies on mosquito vector competence for human pathogens are conducted in laboratory systems that do not consider genetic and/or environmental variability. Evaluating the risk of emergence of arthropod-borne viruses (arboviruses) of public health importance such as chikungunya virus (CHIKV) requires a more realistic appraisal of genetic and environmental contributions to vector competence. In particular, sources of variation do not necessarily act independently and may combine in the form of interactions. Here, we measured CHIKV transmission potential by the mosquito Aedes albopictus in all combinations of six worldwide vector populations, two virus strains and two ambient temperatures (20°C and 28°C). Overall, CHIKV transmission potential by Ae. albopictus strongly depended on the three-way combination of mosquito population, virus strain and temperature. Such genotype-by-genotype-by-environment (G × G × E) interactions question the relevance of vector competence studies conducted with a simpler set of conditions. Our results highlight the need to account for the complex interplay between vectors, pathogens and environmental factors to accurately assess the potential of vector-borne diseases to emerge. 相似文献
70.
Birner-Gruenberger R Susani-Etzerodt H Waldhuber M Riesenhuber G Schmidinger H Rechberger G Kollroser M Strauss JG Lass A Zimmermann R Haemmerle G Zechner R Hermetter A 《Molecular & cellular proteomics : MCP》2005,4(11):1710-1717
Hydrolysis of triacylglycerols and cholesteryl esters is a key event in energy homeostasis of animals. However, many lipolytic activities still await their molecular identification. Here we report on a novel tool for concomitant analysis of lipases in complex proteomes. Fluorescent activity tags mimicking lipid substrates were used to label the proteome of mouse adipose tissue. Analysis by two-dimensional gel electrophoresis and LC-MS/MS led to the identification of all known intracellular lipases as well as a number of novel candidates. One of them was recently shown to be involved in triacylglycerol mobilization in adipocytes and therefore named adipose triglyceride lipase. Functional characterization of expressed enzymes demonstrated that lipolytic and esterolytic activities could be well discriminated. Thus our results show the first map of the lipolytic proteome of mouse adipose tissue and demonstrate the general applicability of our method for rapid profiling and identification of lipolytic activities in complex biological samples. 相似文献