全文获取类型
收费全文 | 1258篇 |
免费 | 113篇 |
出版年
2021年 | 9篇 |
2019年 | 12篇 |
2017年 | 12篇 |
2016年 | 17篇 |
2015年 | 27篇 |
2014年 | 38篇 |
2013年 | 52篇 |
2012年 | 48篇 |
2011年 | 57篇 |
2010年 | 39篇 |
2009年 | 35篇 |
2008年 | 54篇 |
2007年 | 54篇 |
2006年 | 40篇 |
2005年 | 51篇 |
2004年 | 46篇 |
2003年 | 33篇 |
2002年 | 42篇 |
2001年 | 41篇 |
2000年 | 31篇 |
1999年 | 35篇 |
1998年 | 14篇 |
1997年 | 12篇 |
1996年 | 18篇 |
1995年 | 16篇 |
1993年 | 19篇 |
1992年 | 25篇 |
1991年 | 28篇 |
1990年 | 22篇 |
1989年 | 22篇 |
1988年 | 18篇 |
1987年 | 23篇 |
1986年 | 17篇 |
1985年 | 16篇 |
1984年 | 16篇 |
1983年 | 22篇 |
1982年 | 20篇 |
1981年 | 15篇 |
1980年 | 13篇 |
1979年 | 23篇 |
1978年 | 13篇 |
1977年 | 15篇 |
1976年 | 16篇 |
1975年 | 21篇 |
1974年 | 18篇 |
1973年 | 11篇 |
1972年 | 8篇 |
1970年 | 7篇 |
1969年 | 9篇 |
1968年 | 10篇 |
排序方式: 共有1371条查询结果,搜索用时 31 毫秒
91.
The equilibrium structural ensemble of a 20-residue polyglutamic acid peptide (E(20)) was studied with FRET, circular dichroism, and molecular dynamics (MD) simulations. A FRET donor, o-aminobenzamide, and acceptor, 3-nitrotyrosine, were introduced at the N- and C-termini, respectively. Circular dichroism, steady state FRET, and time-resolved FRET measurements were employed to characterize the fraction helix and end-to-end distance under different pH conditions: pH 4 (60% alpha-helix), pH 6 (0% alpha-helix), and pH 9 (0% alpha-helix). At pH 4, the end-to-end distance was measured at 24 A and determined to be considerably less than the 31 A predicted for an alpha-helix of the same length. At pH 6 and 9, the end-to-end distance was measured at > 31 and 39 A respectively, both which are determined to be considerably greater than the 27 A predicted for a freely jointed random coil of the same length. To better understand the physical forces underlying the unusual helix-coil transition in this peptide, three theoretical MD models of E(20) were constructed: (1) a pure alpha-helix, (2) an alpha-helix with equivalent attractive intramolecular contacts, and (3) a weak alpha-helix with termini-weighted intramolecular contacts ("sticky ends"). Using MD simulations, the bent helix structure calculated from Model 3 was found to be the closest in agreement with the experimental data. 相似文献
92.
Badrick AC Hamilton AJ Bernhardt PV Jones CE Kappler U Jennings MP McEwan AG 《FEBS letters》2007,581(24):4663-4667
PrrC is a Sco homologue in Rhodobacter sphaeroides that is associated with PrrBA, a two-component signal transduction system that induces photosynthesis gene expression in response to a decrease in oxygen tension. Although Sco proteins have been shown to bind copper the observation that they are structurally-related to thioredoxins suggested that they might possess thiol-disulfide oxidoreductase activity. Our results show that PrrC reduces Cu(2+) to Cu(+) and possesses disulfide reductase activity. These results indicate that some bacterial Sco proteins may have biochemical properties that are distinct from those of mitochondrial Sco proteins. 相似文献
93.
94.
Sara Santarossa Alexandra R. Sitarik Christine Cole Johnson Jia Li Susan V. Lynch Dennis R. Ownby Alex Ramirez Germaine LM. Yong Andrea E. Cassidy-Bushrow 《Journal of Exercise Nutrition & Biochemistry》2021,25(4):24
[Purpose] To determine whether physical activity (PA), primarily the recommended 60 minutes of moderate-to-vigorous PA, is associated with gut bacterial microbiota in 10-year-old children.[Methods] The Block Physical Activity Screener, which provides minutes/day PA variables, was used to determine whether the child met the PA recommendations. 16S rRNA sequencing was performed on stool samples from the children to profile the composition of their gut bacterial microbiota. Differences in alpha diversity metrics (richness, Pielou’s evenness, and Faith’s phylogenetic diversity) by PA were determined using linear regression, whereas beta diversity (unweighted and weighted UniFrac) relationships were assessed using PERMANOVA. Taxon relative abundance differentials were determined using DESeq2.[Results] The analytic sample included 321 children with both PA and 16S rRNA sequencing data (mean age [SD] =10.2 [0.8] years; 54.2% male; 62.9% African American), where 189 (58.9%) met the PA recommendations. After adjusting for covariates, meeting the PA recommendations as well as minutes/day PA variables were not significantly associated with gut richness, evenness, or diversity (p ≥ 0.19). However, meeting the PA recommendations (weighted UniFrac R2 = 0.014, p = 0.001) was significantly associated with distinct gut bacterial composition. These compositional differences were partly characterized by increased abundance of Megamonas and Anaerovorax as well as specific Christensenellaceae_R-7_group taxa in children with higher PA.[Conclusion] Children who met the recommendations of PA had altered gut microbiota compositions. Whether this translates to a reduced risk of obesity or associated metabolic diseases is still unclear. 相似文献
95.
Interleukin-1 beta (IL-1 beta) is a cytokine and a member of the beta-trefoil superfamily of protein structures. An interesting feature in the folding of IL-1 beta, shared with some other members of the same topological family, is the existence of a slow step in folding to the native conformation from a discrete intermediate. Wanting to probe the nature of this slow step in the folding of WT IL-1 beta (tau(1)=45 seconds), we made ten sequence variants of IL-1 beta (L10A, T9Q, T9G, C8S, C8A, N7G, N7D, L6A, R4P, and R4Q), where all mutations are located along strand 1. This strand is not protected from hydrogen exchange until late in folding. Most of the mutations showed little effect on the kinetics of folding for IL-1 beta. However, C8 is clearly involved in both the late and the early steps in folding, while sequence variants at L10 and L6 affect only late events in folding. The value of the slowest relaxation time, tau(1), which is associated with the rate of native protein formation, increased for the refolding of C8S, while C8A, L6A, and L10A showed smaller but systematic increases in the value of tau(1.)For both C8S and C8A, the value of the step associated with formation of the intermediate, tau(2), was independent of denaturant concentration. In addition, mutations in the hydrophobic core (L10A, C8A, C8S, and L6A) and, surprisingly, along the surface (T9G, T9Q, and N7G) alter the stability. The most destabilizing mutations show changes in equilibrium unfolding cooperativity, which is atypical for destabilizing mutations in IL-1 beta. Crystallographic studies indicate that mutations along strand 1 may alter the number of ordered water molecules within the core. Thus, side-chain replacement in this region can disrupt essential main-chain interactions mediated by ordered water contacts in a highly cooperative network of hydrogen bonding. 相似文献
96.
A fibrinogenase (Ba100) with an apparent molecular mass of 100 kDa under non-reducing conditions and a pI of 5.4 was purified from the venom of the African puff adder (Bitis arietans) by fibrinogen affinity chromatography. Under reducing conditions the protease dissociates into subunits of 21 kDa and 16 kDa. N-Terminal amino acid sequencing showed these two chains to have 66.7% homology and homology to C-type lectins. The fibrinogenase activity of Ba100 cleaves the Aalpha and Bbeta chain of fibrinogen rendering the molecule unable to polymerise into fibrin clots. Ba100 inhibited platelet aggregation in platelet rich plasma, and clot formation in whole blood, in a concentration dependent manner. 相似文献
97.
Newlon MG Roy M Morikis D Hausken ZE Coghlan V Scott JD Jennings PA 《Nature structural biology》1999,6(3):222-227
Compartmentalization of signal transduction enzymes into signaling complexes is an important mechanism to ensure the specificity of intracellular events. Formation of these complexes is mediated by specialized protein motifs that participate in protein-protein interactions. The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) is localized through interaction of the regulatory (R) subunit dimer with A-kinase-anchoring proteins (AKAPs). We now report the solution structure of the type II PKA R-subunit fragment RIIalpha(1-44), which encompasses both the AKAP-binding and dimerization interfaces. This structure incorporates an X-type four-helix bundle dimerization motif with an extended hydrophobic face that is necessary for high-affinity AKAP binding. NMR data on the complex between RIIalpha(1-44) and an AKAP fragment reveals extensive contacts between the two proteins. Interestingly, this same dimerization motif is present in other signaling molecules, the S100 family. Therefore, the X-type four-helix bundle may represent a conserved fold for protein-protein interactions in signal transduction. 相似文献
98.
Zhang C Yang J Jennings LK 《American journal of physiology. Heart and circulatory physiology》2004,287(2):H659-H666
Increased oxidative stress is a major characteristic of restenosis after angioplasty. The oxidative stress is mainly created by oxidants such as reactive oxygen species (ROS), which are assumed to play an important role in neointima formation after angioplasty. DNA is a sensitive target for oxidants; however, oxidative DNA damage remains a poorly examined field in the pathogenesis of restenosis. In the present study, we demonstrated that the expression of the oxidative DNA damage marker 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) was quickly increased in rat carotid arteries after balloon injury. It reached its peak at 14 days after injury and still kept high expression at 28 days after injury. The immunostaining of 8-oxo-dG was present predominantly in the neointima. In response to oxidative DNA damage, the DNA repair enzyme poly(ADP-ribose) polymerase-1 (PARP-1) was significantly increased after balloon injury. The time course change and location of PARP-1 is similar to that of 8-oxo-dG. Daily injections of the PARP-1 inhibitor PJ34 (5 mg.kg(-1).day(-1) ip) attenuated neointima formation by approximately 40% at 7, 14, and 28 days after balloon injury. Treatment with PJ34 inhibited leukocyte infiltration and improved both anatomic (reendothelialization) and functional (endothelial function) recovery of endothelial cells after balloon injury. In conclusion, levels of oxidative DNA damage and the DNA repair enzyme PARP-1 are increased in vessels after balloon injury. Inhibition of PARP-1 attenuates neointima formation through inhibition of leukocyte infiltration and improvement of endothelial cell recovery after balloon injury. Targeting of the DNA repair enzyme might be a therapeutic strategy for restenosis. 相似文献
99.
Rayatt S White N Jennings S Matthews RN 《Plastic and reconstructive surgery》2004,114(2):605-6; author reply 606
100.
The growth of storage moulds was studied in barley at 22% and approximately 28% moisture content treated with the recommended
and reduced commercial doses of propionic acid over a 6 month storage period at 20°C. Experimental sample size was 5 kg barley
per lot. Barley was fully protected against the growth ofA. flavus and aflatoxin formation when the recommended dose was applied. However, the treatment was less effective in controlling growth
ofP. verrucosum and preventing ochratoxin A formation such that by 4 to 6 months of storage, the fungus had started to develop and toxin
had formed even in some of the samples treated with propionic acid. The risk of the development of ochratoxin A during storage
increased as the optimum dose was reduced, particularly for barley at 22% moisture content. 相似文献