全文获取类型
收费全文 | 162篇 |
免费 | 11篇 |
国内免费 | 3篇 |
出版年
2022年 | 1篇 |
2021年 | 3篇 |
2019年 | 3篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 9篇 |
2014年 | 5篇 |
2013年 | 8篇 |
2012年 | 8篇 |
2011年 | 9篇 |
2010年 | 18篇 |
2009年 | 13篇 |
2008年 | 10篇 |
2007年 | 13篇 |
2006年 | 6篇 |
2005年 | 7篇 |
2004年 | 5篇 |
2003年 | 8篇 |
2002年 | 2篇 |
2001年 | 6篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1988年 | 1篇 |
1984年 | 1篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1975年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有176条查询结果,搜索用时 15 毫秒
11.
G Cuce S Cetinkaya N Isitez S Kuccukturk ME Sozen S Kalkan 《Biotechnic & histochemistry》2016,91(2):122-127
Methylmethane sulfonate (MMS) is an alkylating agent that may react with DNA and damage it. We investigated histological changes and apoptosis caused by MMS and the effects of curcumin on MMS treated mouse kidneys. Twenty-four mice were divided into four equal groups: controls injected with saline, a group injected with 40 mg/kg MMS, a group injected with 40 mg/kg MMS and given 100 mg/kg curcumin by gavage, and a group given 100 mg/kg curcumin by gavage. MMS caused congestion and vacuole formation, and elevated the apoptotic index significantly, but had no other effect on kidney tissue. Curcumin improved the congestion and vacuole formation caused by MMS and decreased the apoptotic index. Curcumin administered with MMS appears to decrease the deleterious effects of MMS on the kidney. 相似文献
12.
13.
Singh SB Zink DL Bills GF Teran A Silverman KC Lingham RB Felock P Hazuda DJ 《Bioorganic & medicinal chemistry letters》2003,13(4):713-717
Integration of viral DNA into host cell DNA is an essential step in retroviral (HIV-1) replication and is catalyzed by HIV-1 integrase. HIV-1 integrase is a novel therapeutic target and is the focus of efforts to identify effective inhibitors that will prevent/or cure HIV infections. Four novel naphtho-gamma-pyrones, belonging to the chaetochromin and ustilaginoidin family, were discovered as inhibitors of HIV-1 integrase from the screening of fungal extracts using a recombinant in vitro assay. These compounds inhibit both the coupled and strand transfer activity of HIV-1 integrase with IC(50) values of 1-3 and 4-12 microM, respectively. The discovery, structure elucidation, chemical modification and the structure-activity relationship of these compounds are described. 相似文献
14.
Rod and cone photoreceptors project from the outer retinal surface into a
carbohydrate-rich interphotoreceptor matrix (IPM). Unique IPM
glycoconjugates are distributed around rods and cones. Wheat germ
agglutinin (WGA) strongly decorates the rod matrix domains and weakly
decorates the cone matrix domains. This study characterizes the major
WGA-binding glycoprotein in the human IPM, which we refer to as SPACR
(sialoprotein associated with cones and rods). SPACR, which has a molecular
weight of 147 kDa, was isolated and purified from the IPM by lectin
affinity chromatography. A polyclonal antibody to SPACR was prepared that
colocalizes in tissue preparations with WGA-binding domains in the IPM.
Sequential digestion of SPACR with N- and O- glycosidases results in a
systematic increase in electrophorectic mobility, indicating the presence
of both N- and O-linked glycoconjugates. Complete deglycosylation results
in a reduction in the relative molecular mass of SPACR by about 30%.
Analysis of lectin binding allowed us to identify some of the structural
characteristics of SPACR glycoconjugates. Treatment with neuraminidase
exposes Galbeta1- 3GalNAc disaccharide as indicated by positive peanut
agglutinin (PNA) staining, accompanied by the loss of WGA staining. Maackia
amurensis agglutinins (MAA-1 and MAA-2), specific for sialic acid in
alpha2-3 linkage to Gal, bind SPACR, while Sambucus nigra agglutinin (SNA),
specific for alpha2-6 linked sialic acid, does not, indicating that the
dominant glycoconjugate determinant on SPACR is the O-linked carbohydrate,
NeuAcalpha2-3Galbeta1-3GalNAc. The abundance of sialic acid in SPACR
suggests that this glycoprotein may contribute substantially to the
polyanionic nature of the IPM. The carbohydrate chains present on SPACR
could also provide sites for extensive crosslinking and participate in the
formation of the ordered IPM lattice that surrounds the elongate
photoreceptors projecting from the outer retinal surface.
相似文献
15.
Ricardo Capone Mirela Mustata Hyunbum Jang Fernando Teran Arce Ratnesh Lal 《Biophysical journal》2010,98(11):2644-2652
Antimicrobial peptides (AMPs) are an emerging class of antibiotics for controlling health effects of antibiotic-resistant microbial strains. Protegrin-1 (PG-1) is a model antibiotic among β-sheet AMPs. Antibiotic activity of AMPs involves cell membrane damage, yet their membrane interactions, their 3D membrane-associated structures and the mechanism underlying their ability to disrupt cell membrane are poorly understood. Using complementary approaches, including molecular dynamics simulations, atomic force microscopy (AFM) imaging, and planar lipid bilayer reconstitution, we provide computational and experimental evidence that PG-1, a β-hairpin peptide, forms ion channels. Simulations indicate that PG-1 forms channel-like structures with loosely attached subunits when reconstituted in anionic lipid bilayers. AFM images show the presence of channel-like structures when PG-1 is reconstituted in dioleoylphosphatidylserine/palmitoyloleoyl phosphatidylethanolamine bilayers or added to preformed bilayers. Planar lipid bilayer electrical recordings show multiple single channel conductances that are consistent with the heterogeneous oligomeric channel structures seen in AFM images. PG-1 channel formation seems to be lipid-dependent: PG-1 does not easily show ion channel electrical activity in phosphatidylcholine membranes, but readily shows channel activity in membranes rich in phosphatidylethanolamine or phosphatidylserine. The combined results support a model wherein the β-hairpin PG-1 peptide acts as an antibiotic by altering cell ionic homeostasis through ion channel formation in cell membranes. 相似文献
16.
每搏量变异度是动态的容量监测指标.机械通气患者心肺的相互作用是每搏量变异度的产生基础,通过动脉压力波形分析技术可以进行连续监测.每搏量变异度能够准确预测容量治疗反应,与静态的血流动力学参数相比,对于优化心输出量和组织氧供更有优势,但也存在一定的局限性.每搏量变异度受多种因素影响且不能用于自主呼吸和心律失常的患者.临床应用时应该综合考虑其影响因素,结合其他的指标和方法指导容量治疗. 相似文献
17.
Perez Visñuk Daiana Teran María del Milagro Savoy de Giori Graciela LeBlanc Jean Guy de Moreno de LeBlanc Alejandra 《Neurochemical research》2022,47(5):1269-1279
Neurochemical Research - Oxidative stress and inflammatory processes might contribute to the cascade of events leading Parkinson disease (PD); and vitamins such as riboflavin can exert protection... 相似文献
18.
白马雪山国家级自然保护区典型森林生态系统服务 总被引:1,自引:0,他引:1
生态系统服务是近年来生态学研究的热点领域,对关键区域生态系统服务的研究具有重要意义.云南省白马雪山国家级自然保护区地处青藏高原南延部分,拥有独特的地理位置,是生物多样性保护的热点区域.本文对该保护区森林生态系统的生物量与生产力、水源涵养、营养物质循环等3项服务的功能量进行了评估.结果表明:保护区森林总生物量2215.86×104t,生产力171.84×104t·a-1;水源涵养量11964.56×104m3;N、P、K年吸收量分别为26025.94t、2638.57t、12016.85 t.研究表明,保护区森林生态效益显著,对于维持当地以及周边地区的生态安全具有重要意义. 相似文献
19.
George S. Mahuku María Antonia Henríquez Carmenza Montoya Carlos Jara Henry Teran Stephen Beebe 《Molecular breeding : new strategies in plant improvement》2011,28(1):57-71
Angular leaf spot (ALS) is one of the major diseases of the common bean (Phaseolus vulgaris L.). Different sources of resistance have been identified but few have been characterized. Studies were conducted to elucidate
the inheritance of ALS resistance in the bean accession G10909 and to identify molecular markers linked to these genes. Evaluation
of parental genotypes, F1, F2 and backcross to susceptible parent (Sprite) populations revealed that two dominant and complementary genes conditioned ALS
resistance. Allelism tests showed that the ALS resistance genes in G10909 were different from those in the Mesoamerican cultivars
Mexico 54, MAR 2, G10474 and Cornell 49-242. Three sequence-characterized amplified region (SCAR) markers, PF13310, PF9260 and OPE04709, and a microsatellite, Pv-gaat001, segregated in coupling with the resistance genes in G10909. Pairwise segregation analysis
revealed that markers PF13310, PF9260 and OPE04709 were linked, while Pv-gaat001 segregated in a 9:3:3:1 ratio from all markers. Markers PF13310, PF9260 and OPE04709 were mapped to linkage group B08, and segregated with resistance gene Phg
G10909B
at 4.9, 7.4 and 9.9 cM, respectively. Pv-gaat001, previously mapped to linkage group B04, segregated with resistance gene
Phg
G10909A
at 13 cM. The potential utility of these markers to aid breeding for ALS resistance is discussed. 相似文献
20.
Connelly L Jang H Arce FT Ramachandran S Kagan BL Nussinov R Lal R 《Biochemistry》2012,51(14):3031-3038
Alzheimer's disease (AD) is a misfolded protein disease characterized by the accumulation of β-amyloid (Aβ) peptide as senile plaques, progressive neurodegeneration, and memory loss. Recent evidence suggests that AD pathology is linked to the destabilization of cellular ionic homeostasis mediated by toxic pores made of Aβ peptides. Understanding the exact nature by which these pores conduct electrical and molecular signals could aid in identifying potential therapeutic targets for the prevention and treatment of AD. Here using atomic force microscopy (AFM) and molecular dynamics (MD) simulations, we compared the imaged pore structures with models to predict channel conformations as a function of amino acid sequence. Site-specific amino acid (AA) substitutions in the wild-type Aβ(1-42) peptide yield information regarding the location and significance of individual AA residues to its characteristic structure-activity relationship. We selected two AAs that our MD simulation predicted to inhibit or permit pore conductance. The substitution of Phe19 with Pro has previously been shown to eliminate conductance in the planar lipid bilayer system. Our MD simulations predict a channel-like shape with a collapsed pore, which is supported by the AFM channel images. We suggest that proline, a known β-sheet breaker, creates a kink in the center of the pore and prevents conductance via blockage. This residue may be a viable target for drug development studies aiming to inhibit Aβ from inducing ionic destabilization toxicity. The substitution of Phe20 with Cys exhibits pore structures indistinguishable from the wild type in AFM images. MD simulations predict site 20 to face the solvated pore. Overall, the mutations support the previously predicted β-sheet-based channel structure. 相似文献