全文获取类型
收费全文 | 277篇 |
免费 | 10篇 |
出版年
2024年 | 1篇 |
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 11篇 |
2014年 | 12篇 |
2013年 | 27篇 |
2012年 | 24篇 |
2011年 | 29篇 |
2010年 | 10篇 |
2009年 | 12篇 |
2008年 | 24篇 |
2007年 | 15篇 |
2006年 | 16篇 |
2005年 | 11篇 |
2004年 | 18篇 |
2003年 | 14篇 |
2002年 | 13篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1991年 | 3篇 |
1990年 | 1篇 |
排序方式: 共有287条查询结果,搜索用时 15 毫秒
61.
Sotirios N. Kiokias Charikleia P. Dimakou Ioanna V. Tsaprouni Vassiliki Oreopoulou 《Food biophysics》2006,1(3):115-123
This work attempts to determine any relationship between certain endogenous parameters and the oxidative deterioration of protein-stabilized oil-in-water emulsions. The contribution of compositional factors (e.g., type and amount of emulsifier, fat phase, etc.) is further elucidated. Among 10% cottonseed o/w emulsions prepared by 1% emulsifier (Tween, sodium caseinate, or whey protein), lipid autoxidation (at 40°C) was much faster in the Tween emulsion than in the protein ones, with whey protein presenting a clear antioxidant effect. Increase in protein concentration (0.5–2% w/w) led to a decrease in droplet size but an increase in oxidative stability, in terms of conjugated diene hydroperoxides formation at 232 nm. The type of lipid phase significantly affected the rate of thermal oxidation at 60°C. In the most oxidatively vulnerable sunflower-oil-based emulsions, an increase in fat content (10–40%) resulted in a reduction of oxidative deterioration. By selecting a more concentrated emulsion (20% o/w, 2% emulsifier), in order to structurally approach real novel food products, any influence of the composition of the emulsifier (combination of Tween and sodium caseinate preparation) was subsequently tested. An increase in protein proportion in the emulsifier was found to inhibit proportionally the oxidative instability of the emulsions, as evaluated by the determination of both primary (conjugated diene and lipid hydroperoxides) and secondary [thiobarbituric acid-reactive substances (TBARS)] oxidation products. 相似文献
62.
The N-terminal extracellular domain (ECD; amino acids 1-208) of the neuronal nicotinic acetylcholine receptor (AChR) alpha7 subunit, the only human AChR subunit known to assemble as a homopentamer, was expressed as a glycosylated form in the yeast Pichia pastoris in order to obtain a native-like model of the extracellular part of an intact pentameric nicotinic AChR. This molecule, alpha7-ECD, although able to bind the specific ligand alpha-bungarotoxin, existed mainly in the form of microaggregates. Substitution of Cys-116 in the alpha7-ECD with serine led to a decrease in microaggregate size. A second mutant form, alpha7-ECD(C116S,Cys-loop), was generated in which, in addition to the C116S mutation, the hydrophobic Cys-loop (Cys(128)-Cys(142)) was replaced by the corresponding hydrophilic Cys-loop from the snail glial cell acetylcholine-binding protein. This second mutant protein was water-soluble, expressed at a moderate level (0.5 +/- 0.1 mg/liter), and had a size corresponding approximately to a pentamer as judged by gel filtration and electron microscopy studies. It also bound (125)I-alpha-bungarotoxin with relatively high affinity (K(d) = 57 nm), the binding being inhibited by unlabeled alpha-bungarotoxin, d-tubocurarine, or nicotine (K(i) = 0.8 x 10(-7) m, K(i) = 1 x 10(-5) m, and K(i) = 0.9 x 10(-2) m, respectively). All three constructs were expressed as glycosylated forms, but in vitro deglycosylation reduced the heterogeneity without affecting their ligand binding properties. These results show that alpha7-ECD(C116S,Cys-loop) was expressed in P. pastoris as an oligomer (probably a pentamer) with a near native conformation and that its deglycosylated form seems to be suitable starting material for structural studies on the ligand-binding domain of a neurotransmitter receptor. 相似文献
63.
We report the solid phase synthesis and some pharmacological properties of seventeen new oxytocin (OT) analogues. Basic modification at positions 8 and/or 9 (introduction of L-alpha-t-butylglycine [Gly(Bu(t))]) was combined with D-Cys(6), D-Tyr(Et)(2), Mpa(1) or Pen(1) modifications and their various combinations. We also present properties of two previously reported re-synthesized analogues ([Gly(Bu(t))(8)]OT and [Mpa(1), Gly(Bu(t))(8)]OT). The analogues were tested for rat uterotonic activity in vitro, in the rat pressor assay and for binding affinity to human OTR. 相似文献
64.
65.
Evolution of divergent DNA recognition specificities in VDE homing endonucleases from two yeast species 总被引:3,自引:1,他引:2
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Homing endonuclease genes (HEGs) are mobile DNA elements that are thought to confer no benefit to their host. They encode site-specific DNA endonucleases that perpetuate the element within a species population by homing and disseminate it between species by horizontal transfer. Several yeast species contain the VMA1 HEG that encodes the intein-associated VMA1-derived endonuclease (VDE). The evolutionary state of VDEs from 12 species was assessed by assaying their endonuclease activities. Only two enzymes are active, PI-ZbaI from Zygosaccharomyces bailii and PI-ScaI from Saccharomyces cariocanus. PI-ZbaI cleaves the Z.bailii recognition sequence significantly faster than the Saccharomyces cerevisiae site, which differs at six nucleotide positions. A mutational analysis indicates that PI-ZbaI cleaves the S.cerevisiae substrate poorly due to the absence of a contact that is analogous to one made in PI-SceI between Gln-55 and nucleotides +9/+10. PI-ZbaI cleaves the Z.bailii substrate primarily due to a single base-pair substitution (A/T+5 → T/A+5). Structural modeling of the PI-ZbaI/DNA complex suggests that Arg-331, which is absent in PI-SceI, contacts T/A+5, and the reduced activity observed in a PI-ZbaI R331A mutant provides evidence for this interaction. These data illustrate that homing endonucleases evolve altered specificity as they adapt to recognize alternative target sites. 相似文献
66.
This paper attempts a critical examination of scholarly understanding of the historical event referred to as the Darwinian Revolution. In particular, it concentrates on some of the major scholarly works that have appeared since the publication in 1979 of Michael Ruses The Darwinian Revolution: Nature Red in Tooth and Claw. The paper closes by arguing that fruitful critical perspectives on what counts as this event can be gained by locating it in a range of historiographic and disciplinary contexts that include the emergence of the discipline of evolutionary biology (following the evolutionary synthesis), the 1959 Darwin centenary, and the maturation of the discipline of the history of science. Broader perspectives on something called the Darwinian Revolution are called for that include recognizing that it does not map a one-to-one correspondence with the history of evolution, broadly construed. 相似文献
67.
68.
Lafuente EM van Puijenbroek AA Krause M Carman CV Freeman GJ Berezovskaya A Constantine E Springer TA Gertler FB Boussiotis VA 《Developmental cell》2004,7(4):585-595
The small GTPase Rap1 induces integrin-mediated adhesion and changes in the actin cytoskeleton. The mechanisms that mediate these effects of Rap1 are poorly understood. We have identified RIAM as a Rap1-GTP-interacting adaptor molecule. RIAM defines a family of adaptor molecules that contain a RA-like (Ras association) domain, a PH (pleckstrin homology) domain, and various proline-rich motifs. RIAM also interacts with Profilin and Ena/VASP proteins, molecules that regulate actin dynamics. Overexpression of RIAM induced cell spreading and lamellipodia formation, changes that require actin polymerization. In contrast, RIAM knockdown cells had reduced content of polymerized actin. RIAM overexpression also induced integrin activation and cell adhesion. RIAM knockdown displaced Rap1-GTP from the plasma membrane and abrogated Rap1-induced adhesion. Thus, RIAM links Rap1 to integrin activation and plays a role in regulating actin dynamics. 相似文献
69.
In the present study we demonstrated that synaptosomes isolated from rabbit brain cortex contain NO synthase and xanthine
oxidase that can be activated by ultraviolet B radiation and Ca2+ accumulation to produce nitric oxide and superoxide which react together to form peroxynitrite. Irradiation of synaptosomes
with ultraviolet B (up to 100 mJ/cm2), or increase the intrasynaptosomal calcium concentration using various doses (up to 100 μM) of the calcium ionophore A 23187,
a gradual increase in both nitric oxide and peroxynitrite release that was inhibited by N-monomethyl-L-arginine (100 μM) was
observed. The rate of nitric oxide release and cyclic GMP production by NO synthase and soluble guanylate cyclase, both located
in the soluble fraction of synaptosomes (synaptosol), were increased approximately eight fold after treatment of synaptosomes
with Ultraviolet B radiation (100 mJ/cm2). In reconstitution experiments, when purified NO synthase isolated from synaptosol was added to xanthine oxidase, in the
presence of the appropriate cofactors and substrates, a ten fold increase in peroxynitrite production at various doses (up
to 20 mJ/cm2) of UVB radiation was observed. Ultraviolet B irradiated synaptosomes promptly increased malondialdehyde production with
subsequent decrease of synaptosomal plasma membrane fluidity estimated by fluorescence anisotropy of 1-4-(trimethyl-amino-phenyl)-6-phenyl-hexa-1,3,5-triene.
Desferrioxamine (100 μM) tested in Ultraviolet B-irradiated synaptosomes showed a decrease (approximately 80%) in malondialdehyde
production with subsequent restoration of the membrane fluidity to that of non-irradiated (control) synaptosomes. Ca2+-stimulated ATPase activity was decreased after Ultraviolet B (100 mJ/cm2) radiation of synaptosomes indicating that the subsequent increase of intrasynaptosomal calcium promoted peroxynitrite production
by a calmodulin-dependent increase of NO synthase and xanthine oxidase activities. Furthermore, it was shown that UVB-irradiated
synaptosomes were subjected to higher oxidative stress by exogenous peroxynitrite (100 μM) compared to non-irradiated (control)
synaptosomes. In summary, the present results indicate that activation of NO synthase and xanthine oxidase of brain cells
lead to the formation of peroxynitrite providing important clues in the role of peroxynitrite as a causative factor in neurotoxicity. 相似文献
70.
George Papaxoinis Vassiliki Kotoula Zoi Alexopoulou Konstantine T. Kalogeras Flora Zagouri Eleni Timotheadou Helen Gogas George Pentheroudakis Christos Christodoulou Angelos Koutras Dimitrios Bafaloukos Gerasimos Aravantinos Pavlos Papakostas Elpida Charalambous Kyriaki Papadopoulou Ioannis Varthalitis Ioannis Efstratiou Thomas Zaramboukas Helen Patsea Chrisoula D. Scopa Maria Skondra Paris Kosmidis Dimitrios Pectasides George Fountzilas 《PloS one》2015,10(10)