全文获取类型
收费全文 | 253篇 |
免费 | 17篇 |
专业分类
270篇 |
出版年
2023年 | 1篇 |
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 7篇 |
2016年 | 7篇 |
2015年 | 9篇 |
2014年 | 14篇 |
2013年 | 18篇 |
2012年 | 18篇 |
2011年 | 21篇 |
2010年 | 9篇 |
2009年 | 9篇 |
2008年 | 13篇 |
2007年 | 13篇 |
2006年 | 15篇 |
2005年 | 14篇 |
2004年 | 16篇 |
2003年 | 14篇 |
2002年 | 24篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1993年 | 1篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1985年 | 1篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1977年 | 3篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有270条查询结果,搜索用时 15 毫秒
21.
Yuan S Yu X Topf M Dorstyn L Kumar S Ludtke SJ Akey CW 《Structure (London, England : 1993)》2011,19(1):128-140
The Drosophila Apaf-1 related killer forms an apoptosome in the intrinsic cell death pathway. In this study we show that Dark forms a single ring when initiator procaspases are bound. This Dark-Dronc complex cleaves DrICE efficiently; hence, a single ring represents the Drosophila apoptosome. We then determined the 3D structure of a double ring at ~6.9?? resolution and created a model of the apoptosome. Subunit interactions in the Dark complex are similar to those in Apaf-1 and CED-4 apoptosomes, but there are significant differences. In particular, Dark has "lost" a loop in the nucleotide-binding pocket, which opens a path for possible dATP exchange in the apoptosome. In addition, caspase recruitment domains (CARDs) form a crown on the central hub of the Dark apoptosome. This CARD geometry suggests that conformational changes will be required to form active Dark-Dronc complexes. When taken together, these data provide insights into apoptosome structure, function, and evolution. 相似文献
22.
The use of models to predict indoor air quality and health risk for the soil vapor transport to indoor air pathway is commonplace; however, there is significant uncertainty surrounding processes and factors affecting this pathway, and the accuracy of models used. Available screening models were evaluated through a review of model characteristics and sensitivity, and through comparisons to measured conditions at field sites. Model simulations and comparisons to field data indicate that the vapor attenuation ratio (α) is highly sensitive to certain processes (e.g., biodegradation and ad-vection) and input parameters. Comparisons of model predicted to measured a values indicate that models based on the Johnson and Ettinger (1991) framework in most cases result in predictions that are conservative by up to one to two orders of magnitude for field sites that were assessed, providing that appropriate input parameters are used. However, for sites where the advection potential is high, these models may not be conservative. The potential for advective transport of vapors into building may be significant for sites with shallow contamination, high permeability soil and foundation and high building underpressurization. The paper concludes with possible tiered management framework for the soil vapor pathway. 相似文献
23.
Cicchillo RM Iwig DF Jones AD Nesbitt NM Baleanu-Gogonea C Souder MG Tu L Booker SJ 《Biochemistry》2004,43(21):6378-6386
Lipoyl synthase (LipA) catalyzes the formation of the lipoyl cofactor, which is employed by several multienzyme complexes for the oxidative decarboxylation of various alpha-keto acids, as well as the cleavage of glycine into CO(2) and NH(3), with concomitant transfer of its alpha-carbon to tetrahydrofolate, generating N(5),N(10)-methylenetetrahydrofolate. In each case, the lipoyl cofactor is tethered covalently in an amide linkage to a conserved lysine residue located on a designated lipoyl-bearing subunit of the complex. Genetic and biochemical studies suggest that lipoyl synthase is a member of a newly established class of metalloenzymes that use S-adenosyl-l-methionine (AdoMet) as a source of a 5'-deoxyadenosyl radical (5'-dA(*)), which is an obligate intermediate in each reaction. These enzymes contain iron-sulfur clusters, which provide an electron during the cleavage of AdoMet, forming l-methionine in addition to the primary radical. Recently, one substrate for lipoyl synthase has been shown to be the octanoylated derivative of the lipoyl-bearing subunit (E(2)) of the pyruvate dehydrogenase complex [Zhao, S., Miller, J. R., Jian, Y., Marletta, M. A., and Cronan, J. E., Jr. (2003) Chem. Biol. 10, 1293-1302]. Herein, we show that the octanoylated derivative of the lipoyl-bearing subunit of the glycine cleavage system (H-protein) is also a substrate for LipA, providing further evidence that the cofactor is synthesized on its target protein. Moreover, we show that the 5'-dA(*) acts directly on the octanoyl substrate, as evidenced by deuterium transfer from [octanoyl-d(15)]H-protein to 5'-deoxyadenosine. Last, our data indicate that 2 equiv of AdoMet are cleaved irreversibly in forming 1 equiv of [lipoyl]H-protein and are consistent with a model in which two LipA proteins are required to synthesize one lipoyl group. 相似文献
24.
Loretta DiPietro James Dziura Catherine W Yeckel P Darrell Neufer 《Journal of applied physiology》2006,100(1):142-149
Few studies have compared the relative benefits of moderate- vs. higher intensity exercise training on improving insulin sensitivity in older people while holding exercise volume constant. Healthy older (73 +/- 10 yr) women (N = 25) who were inactive, but not obese, were randomized into one of three training programs (9-mo duration): 1) high-intensity [80% peak aerobic capacity (V(O2)peak); T(H)] aerobic training; 2) moderate-intensity (65% V(O2)peak; T(M)) aerobic training; or 3) low-intensity (stretching) placebo control (50% V(O2)peak); C(TB)). Importantly, exercise volume (300 kcal/session) was held constant for subjects in both the T(H) and the T(M) groups. V(O2)peak was determined by using a graded exercise challenge on a treadmill. Total body fat and lean mass were determined with dual-energy X-ray absorptiometry. The rate of insulin-stimulated glucose utilization as well as the suppression of lipolysis were determined approximately 72 h after the final exercise bout by using a two-step euglycemic-hyperinsulinemic clamp. We observed improved glucose utilization at the higher insulin dose with training, but these improvements were statistically significant only in the T(H) (21%; P = 0.02) compared with the T(M) (16%; P = 0.17) and C(TB) (8%; P = 0.37) groups and were observed without changes in either body composition or V(O2)peak. Likewise in the T(H) group, we detected a significant improvement in insulin-stimulated suppression (%) of adipose tissue lipolysis at the low-insulin dose (38-55%, P < 0.05). Our findings suggest that long-term higher intensity exercise training provides more enduring benefits to insulin action compared with moderate- or low-intensity exercise, likely due to greater transient effects. 相似文献
25.
Chegaev K Lazzarato L Tron GC Marabello D Stilo AD Cena C Fruttero R Gasco A Vanthuyne N Roussel C 《Chirality》2006,18(6):430-436
As an introductory study of in vitro vasodilating activity, the access to the four stereomers of 1-phenylglyceryl trinitrate is described using achiral and chiral chromatography. For semi-preparative separation of the enantiomers, a Chiralcel OD (250 x 10 mm, 10 microm) was used. Catalytic reduction leading to the corresponding stereomers of 1-phenylglycerol allowed absolute configuration assignments. The same methods were used for the separation and configuration assignment of the enantiomers of 3-phenylpropane-1,2-diyl dinitrate. 相似文献
26.
Soil Carbon, Nitrogen and Phosphorus Dynamics as Affected by Solarization Alone or Combined with Organic Amendment 总被引:1,自引:0,他引:1
Antonio Gelsomino Luigi Badalucco Loretta Landi Giovanni Cacco 《Plant and Soil》2006,279(1-2):307-325
Soil solarization, alone or combined with organic amendment, is an increasingly attractive approach for managing soil-borne
plant pathogens in agricultural soils. Even though it consists in a relatively mild heating treatment, the increased soil
temperature may strongly affect soil microbial processes and nutrients dynamics. This study aimed to investigate the impact
of solarization, either with or without addition of farmyard manure, in soil dynamics of various C, N and P pools. Changes
in total C, N and P contents and in some functionally-related labile pools (soil microbial biomass C and N, K2SO4-extractable C and N, basal respiration, KCl-exchangeable ammonium and nitrate, and water-soluble P) were followed across
a 72-day field soil solarization experiment carried out during a summer period on a clay loam soil in Southern Italy. Soil
physico-chemical properties (temperature, moisture content and pH) were also monitored. The average soil temperature at 8-cm
depth in solarized soils approached 55 °C as compared to 35 °C found in nonsolarized soil. Two-way ANOVA (solarization×organic
amendment) showed that both factors significantly affected most of the above variables, being the highest influence exerted
by the organic amendment. With no manure addition, solarization did not significantly affect soil total C, N and P pools.
Whereas soil pH, microbial biomass and, at a greater extent, K2SO4-extractable N and KCl-exchangeable ammonium were greatly affected. An increased release of water-soluble P was also found
in solarized soils. Yet, solarization altered the quality of soluble organic residues released in soil as it lowered the C-to-N
ratio of both soil microbial biomass and K2SO4-extractable organic substrates. Additionally, in solarized soils the metabolic quotient (qCO2) significantly increased while the microbial biomass C-to-total organic C ratio (microbial quotient) decreased over the whole
time course. We argued that soil solarization promoted the mineralization of readily decomposable pools of the native soil
organic matter (e.g. the microbial biomass) thus rendering larger, at least over a short-term, the available fraction of some
soil mineral nutrients, namely N and P forms. However, over a longer prospective solarization may lead to an over-exploitation
of labile organic resources in agricultural soils. Manure addition greatly increased the levels of both total and labile C,
N and P pools. Thus, addition of organic amendments could represent an important strategy to protect agricultural lands from
excessive soil resources exploitation and to maintain soil fertility while enhancing pest control. 相似文献
27.
Loretta Ma Fumin Dong Maryam Zaid Ashok Kumar Xiaohui Zha 《The Journal of biological chemistry》2012,287(48):40502-40512
Nonresolving inflammatory response from macrophages is a major characteristic of atherosclerosis. Macrophage ABCA1 has been previously shown to suppress the secretion of proinflammatory cytokine. In the present study, we demonstrate that ABCA1 also promotes the secretion of IL-10, an anti-inflammatory cytokine critical for inflammation resolution. ABCA1+/+ bone marrow-derived macrophages secrete more IL-10 but less proinflammatory cytokines than ABCA1−/− bone marrow-derived macrophages, similar to alternatively activated (M2) macrophages. We present evidence that ABCA1 activates PKA and that this elevated PKA activity contributes to M2-like inflammatory response from ABCA1+/+ bone marrow-derived macrophages. Furthermore, cholesterol lowering by statins, methyl-β-cyclodextrin, or filipin also activates PKA and, consequently, transforms macrophages toward M2-like phenotype. Conversely, cholesterol enrichment suppresses PKA activity and promotes M1-like inflammatory response. As the primary function of ABCA1 is cholesterol removal, our results suggest that ABCA1 activates PKA by regulating cholesterol. Indeed, forced cholesterol enrichment in ABCA1-expressing macrophages suppresses PKA activation and elicits M1-like response. Collectively, these findings reveal a novel protective process by ABCA1-activated PKA in macrophages. They also suggest cholesterol lowering in extra-hepatic tissues by statins as an anti-inflammation strategy. 相似文献
28.
Rolando B Filieri A Chegaev K Lazzarato L Giorgis M De Nardi C Fruttero R Martel S Carrupt PA Gasco A 《Bioorganic & medicinal chemistry》2012,20(2):841-850
A new class of co-drugs were synthesised by joining antioxidant edaravone with a vasodilating substructure containing NO-donor nitrooxy functions, and characterised for their stability in different media, lipophilicity and permeability profile. The products display good stability in water/co-solvent at different pH. Conversely, they are rapidly metabolised into edaravone and NO-donor moieties when incubated in human serum or rat-liver homogenates. In the latter conditions time dependent production of nitrite/nitrate (NO(x)) occurs. The compounds display wide-ranging lipophilicity. PAMPA studies predict good gastrointestinal absorption for a number of these compounds. The title products are potentially useful for treating ROS-related conditions accompanied by decreased NO availability. 相似文献
29.
Wilanowski T Caddy J Ting SB Hislop NR Cerruti L Auden A Zhao LL Asquith S Ellis S Sinclair R Cunningham JM Jane SM 《The EMBO journal》2008,27(6):886-897
In Drosophila, the grainy head (grh) gene plays a range of key developmental roles through the regulation of members of the cadherin gene family. We now report that mice lacking the grh homologue grainy head-like 1 (Grhl1) exhibit hair and skin phenotypes consistent with a reduction in expression of the genes encoding the desmosomal cadherin, desmoglein 1 (Dsg1). Grhl1-null mice show an initial delay in coat growth, and older mice exhibit hair loss as a result of poor anchoring of the hair shaft in the follicle. The mice also develop palmoplantar keratoderma, analogous to humans with DSG1 mutations. Sequence analysis, DNA binding, and chromatin immunoprecipitation experiments demonstrate that the human and mouse Dsg1 promoters are direct targets of GRHL1. Ultrastructural analysis reveals reduced numbers of abnormal desmosomes in the interfollicular epidermis. These findings establish GRHL1 as an important regulator of the Dsg1 genes in the context of hair anchorage and epidermal differentiation, and suggest that cadherin family genes are key targets of the grainy head-like genes across 700 million years of evolution. 相似文献
30.