全文获取类型
收费全文 | 228篇 |
免费 | 12篇 |
专业分类
240篇 |
出版年
2021年 | 6篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 8篇 |
2017年 | 4篇 |
2016年 | 9篇 |
2015年 | 2篇 |
2014年 | 11篇 |
2013年 | 16篇 |
2012年 | 12篇 |
2011年 | 9篇 |
2010年 | 16篇 |
2009年 | 16篇 |
2008年 | 16篇 |
2007年 | 15篇 |
2006年 | 13篇 |
2005年 | 9篇 |
2004年 | 4篇 |
2003年 | 11篇 |
2002年 | 9篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1984年 | 4篇 |
1980年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1929年 | 2篇 |
1927年 | 1篇 |
排序方式: 共有240条查询结果,搜索用时 0 毫秒
141.
Galya Staneva Diana Petkova Rusina Hazarosova Rayna Georgieva Roumen Pankov Ralica Skrobanska Albena Momchilova 《Food biophysics》2014,9(2):138-144
Xylooligosaccharides (XOS) are non-digestible carbohydrate prebiotics that beneficially affect the host by selective stimulation of specific bacteria in the gastro-intestinal tract. The impact of XOS on gastrointestinal microflora and blood lipids is well known but the exact mechanism of action on liver membranes is still unclear. The organization of membrane lipids in domains is known to be important for the proper functioning of various receptors and mechanisms triggering cell signaling. In this study the influence of XOS-enriched diet on the lipid bilayer structure of rat liver plasma membrane was investigated. XOS intake caused a slight decrease of the fluidity of lipid extracts from liver plasma membranes compared to the controls. This observation was based on the increased generalized polarization (GP) and blue shifted emission spectra of Laurdan. The elevated amount of membrane sphingomyelin may be one possible reason for the reported effects. The micron-scale phase separation of the lipid extracts was also investigated by fluorescence microscopy. A different temperature of phase separation and domain pattern was observed in plasma membrane lipid extracts from XOS-fed animals. We presume that it could be assigned to the altered lipid composition of the membrane bilayer, in particular to the changes in the sphingomyelin/cholesterol ratio. All observed alterations are discussed in the light of the impact of XOS on human health and physiology. 相似文献
142.
143.
144.
Vasily I. Radashevsky Yana N. Alexandrova Olga V. Yurchenko 《Invertebrate reproduction & development.》2013,57(3):168-174
Adults of Aonides oxycephala, common inhabitants of shallow boreal waters in the Atlantic and Pacific Oceans, release gametes into the water where fertilization and lecithotrophic larval development occur. During spermiogenesis, the acrosomal vesicle migrates from the posterior to the anterior end of the spermatid and the number of mitochondria reduces from six in early spermatids to four in mature spermatozoa. Each spermatozoon has an ovoid head with the acrosome 1.4?±?0.1?µm long and 1.6?±?0.1?µm wide and the nucleus 1.7?±?0.1?µm long and 2.3?±?0.1?µm in diameter, four spherical mitochondria, two centrioles oriented perpendicular to each other, putative glycogen in the shape of dense granules in the midpiece, and a flagellum with 9?×?2?+?2 organization of microtubules. The acrosome is a complex heterogeneous structure with five ordered layers of different electron densities, lying in a shallow depression on the anterior end of the nucleus. The nucleus is barrel-shaped (truncated ovoid) with the centriolar fossa housing the distal and proximal centrioles. Spermiogenesis and ultrastructure of spermatozoa of A. oxycephala are similar to those of another free spawning spionid, Marenzelleria viridis. Aonides and Marenzelleria have not, however, been considered as closely related taxa; thus, similarity in the morphology of their sperm might result from convergence or parallelism. 相似文献
145.
Albena Alexandrova Lubomir Petrov Margarita Kirkova 《Central European Journal of Biology》2006,1(2):289-298
Numerous studies have indicated that oxidative stress contributes to the development and progression of diabetes and other
related complications. Since the ubiquitin-proteasome pathway is involved in degradation of oxidized proteins, it is to be
expected that alterations in proteasome-dependent proteolysis accompany diabetes. This paper focuses on the role of the proteasome
in alloxan-induced experimental diabetes. The changes in proteasomal activity and oxidative stress indices (protein oxidation
and lipid peroxidation) were evaluated. The obtained results revealed increased protein oxidation and lipid peroxidation,
as well as alterations in proteasomal activities in diabetic rats. Our data indicates a significant decrease in chymotryptic-like
activity; increased tryptic-like activity; and unchanged post-glutamyl peptide hydrolytic-like activity. These findings suggest
the presence of oxidative stress in diabetes that appears to result in changes to the ubiquitin-proteasome pathway. 相似文献
146.
De Pourcq K Vervecken W Dewerte I Valevska A Van Hecke A Callewaert N 《Microbial cell factories》2012,11(1):53
ABSTRACT: BACKGROUND: Protein-based therapeutics represent the fastest growing class of compounds in the pharmaceutical industry. This has created an increasing demand for powerful expression systems. Yeast systems are widely used, convenient and cost-effective. Yarrowia lipolytica is a suitable host that is generally regarded as safe (GRAS). Yeasts, however, modify their glycoproteins with heterogeneous glycans containing mainly mannoses, which complicates downstream processing and often interferes with protein function in man. Our aim was to glyco-engineer Y. lipolytica to abolish the heterogeneous, yeast-specific glycosylation and to obtain homogeneous human high-mannose type glycosylation. RESULTS: We engineered Y. lipolytica to produce homogeneous human-type terminal-mannose glycosylated proteins, i.e. glycosylated with Man8GlcNAc2 or Man5GlcNAc2. First, we inactivated the yeast-specific Golgi alpha-1,6-mannosyltransferases YlOch1p and YlMnn9p; the former inactivation yielded a strain producing homogeneous Man8GlcNAc2 glycoproteins. We tested this strain by expressing glucocerebrosidase and found that the hypermannosylation-related heterogeneity was eliminated. Furthermore, detailed analysis of N-glycans showed that YlOch1p and YlMnn9p, despite some initial uncertainty about their function, are most likely the alpha-1,6-mannosyltransferases responsible for the addition of the first and second mannose residue, respectively, to the glycan backbone. Second, introduction of an ER-retained alpha-1,2-mannosidase yielded a strain producing proteins homogeneously glycosylated with Man5GlcNAc2. The use of the endogenous LIP2pre signal sequence and codon optimization greatly improved the efficiency of this enzyme. CONCLUSIONS: We generated a Y. lipolytica expression platform for the production of heterologous glycoproteins that are homogenously glycosylated with either Man8GlcNAc2 or Man5GlcNAc2 N-glycans. This platform expands the utility of Y. lipolytica as a heterologous expression host and makes it possible to produce glycoproteins with homogeneously glycosylated N-glycans of the human high-mannose-type, which greatly broadens the application scope of these glycoproteins. 相似文献
147.
148.
Nadezhda Stefanova Galya Staneva Diana Petkova Teodora Lupanova Roumen Pankov Albena Momchilova 《Cell biology international》2009,33(10):1079-1086
Most in vitro studies use 2-dimensional (2D) monolayer cultures, where cells are forced to adjust to unnatural substrates that differ significantly from the natural 3-dimensional (3D) extracellular matrix that surrounds cells in living organisms. Our analysis demonstrates significant differences in the cholesterol and sphingomyelin content, structural organization and cholesterol susceptibility to oxidation of plasma membranes isolated from cells cultured in 3D cultures compared with conventional 2D cultures. Differences occurred in the asymmetry of cholesterol molecules and the physico-chemical properties of the 2 separate leaflets of plasma membranes in 2D and 3D cultured fibroblasts. Transmembrane distribution of other membrane phospholipids was not different, implying that the cholesterol asymmetry could not be attributed to alterations in the scramblase transport system. Differences were also established in the chemical activity of cholesterol, assessed by its susceptibility to cholesterol oxidase in conventional and “matrix” cell cultures. The influence of plasma membrane sphingomyelin and phospholipid content on cholesterol susceptibility to oxidation in 2D and 3D cells was investigated with exogenous sphingomyelinase (SMase) and phospholipase C (PLC) treatment. Sphingomyelin was more effective than membrane phospholipids in protecting cholesterol from oxidation. We presume that the higher cholesterol/sphingomyelin molar ratio is the reason for the higher rate of cholesterol oxidation in plasma membranes of 3D cells. 相似文献
149.
Albena Jordanova Nadezhda Stefanova Galya Staneva Roumen Pankov Albena Momchilova Zdravko Lalchev 《Cell biochemistry and biophysics》2009,54(1-3):47-55
The differences in the surface active properties of native lipids extracted from plasma membranes of cells cultured as a monolayer and in three-dimensional (3D) matrix were investigated. This experimental model was chosen because most of the current knowledge on cellular physiological processes is based on studies performed with conventional monolayer two-dimensional (2D) cell cultures, where cells are forced to adjust to unnaturally rigid surfaces that differ significantly from the natural matrix surrounding cells in living organisms. Differences between monolayer and 3D cells were observed in the lipid composition of plasma membranes and especially in the level of the two major microdomain-forming lipids—sphingomyelin (SM) and cholesterol, which were significantly elevated in 3D cells. The obtained results showed that culturing of cells in in vivo-like environment affected the surface active properties of plasma membrane lipids at interfaces which might influence certain membrane-associated interface processes. The detected differences in the lipid levels in 2D and 3D cell extracts affected significantly the behavior of the model lipid monolayers at the air–water interface (Langmuir monolayers) which resulted in different values of the monolayer equilibrium (γeq) and dynamic (γmax, γmin) surface tension and surface potential. Compensation of the SM content in extracts of 2D cell cultures up to a level close to the one measured in 3D cells approximated the monolayer properties to the values observed for 3D cells. These results implied that the interactions between the cells and the surrounding medium affected the level of plasma membrane SM and other lipids, which had a strong impact on the surface properties of lipid monolayers, such as γeq, γmax, and γmin, the compression/decompression curve shape, the hysteresis area during cycling of the monolayers, etc. We suggest that the elevated content of SM observed in plasma membranes of 3D fibroblasts could be responsible for an increased rigidity and possibly reduced permeability of cells cultured in 3D environment. The current results provide useful information that should be taken into account in the interpretation of the membrane physico-chemical properties of cells cultured under different conditions. 相似文献
150.
Rizaldi Sistiabudi John Paderi Alyssa Panitch Albena Ivanisevic 《Biotechnology and bioengineering》2009,102(6):1723-1729
Current efforts to reverse loss of visual function due to Age‐related Macular Degeneration point to the restoration of the Retinal Pigment Epithelial (RPE) layer. Restoration of the RPE layer involves replacing lost RPE cells as well as addressing the degeneration of the underlying Bruch's membrane (BM). To advance the potential of using donor BM, we present a strategy to achieve specific and controllable modification of the inner collagenous layer (ICL) of the Bruch's membrane. In particular, interaction between a collagen binding peptide (CBP) sequence with exposed collagen fibers on the ICL surface is utilized to anchor bioactive molecules. Here, a cell‐adhesion sequence is added to the collagen binding sequence to promote attachment and survival of ARPE‐19. First, the binding specificity of the CBP sequence is verified with a fluorescent binding assay. Subsequently, the effect of modification using the peptide is studied qualitatively using confocal fluorescent imaging and quantitatively through a cell proliferation assay. Results of these experiments indicate that the peptide sequence binds specifically to collagen fibers. Additionally, modification using the peptide enhanced cell adhesion, allowing large uniform cell networks to be formed on the surface. Furthermore, modification with the peptide also delayed the onset of apoptosis on adherent cells. Biotechnol. Bioeng. 2009;102: 1723–1729. © 2008 Wiley Periodicals, Inc. 相似文献