全文获取类型
收费全文 | 1079篇 |
免费 | 76篇 |
国内免费 | 47篇 |
专业分类
1202篇 |
出版年
2024年 | 1篇 |
2023年 | 17篇 |
2022年 | 19篇 |
2021年 | 57篇 |
2020年 | 30篇 |
2019年 | 63篇 |
2018年 | 44篇 |
2017年 | 39篇 |
2016年 | 50篇 |
2015年 | 66篇 |
2014年 | 72篇 |
2013年 | 56篇 |
2012年 | 86篇 |
2011年 | 84篇 |
2010年 | 43篇 |
2009年 | 44篇 |
2008年 | 66篇 |
2007年 | 57篇 |
2006年 | 47篇 |
2005年 | 26篇 |
2004年 | 30篇 |
2003年 | 32篇 |
2002年 | 32篇 |
2001年 | 20篇 |
2000年 | 16篇 |
1999年 | 20篇 |
1998年 | 10篇 |
1997年 | 9篇 |
1996年 | 10篇 |
1995年 | 13篇 |
1994年 | 7篇 |
1993年 | 8篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 6篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有1202条查询结果,搜索用时 15 毫秒
91.
SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis 总被引:11,自引:0,他引:11
Kim D Nguyen MD Dobbin MM Fischer A Sananbenesi F Rodgers JT Delalle I Baur JA Sui G Armour SM Puigserver P Sinclair DA Tsai LH 《The EMBO journal》2007,26(13):3169-3179
A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention. 相似文献
92.
Lanter JC Fiordeliso JJ Alford VC Zhang X Wells KM Russell RK Allan GF Lai MT Linton O Lundeen S Sui Z 《Bioorganic & medicinal chemistry letters》2007,17(9):2545-2548
Through an in vivo screening model, we developed the in vivo SAR of beta-alkylthio indolyl carbinols. Through these efforts we identified a compound with potent oral in vivo efficacy in both immature and mature rat prostate weight reduction models and in a murine xenograft prostate cancer model. 相似文献
93.
The quality of pharmaceutical products such as ginseng is important for ensuring consumer safety and efficacy. Ginseng is
an expensive herb, and adulteration with other cheaper products may occur. Quality assurance of ginseng is needed since many
of its commercial products now come in various formulations such as capsules, powder, softgels and tea. Thus traditional means
of authentication via smell, taste or physical appearance are hardly reliable. Herbs like ginseng tend to exhibit characteristic
infrared fingerprints due to their different chemical constituents. Here we report for the first time a rapid means of distinguishing
American and Asian ginsengs from two morphological fakes – sawdust and Platycodon grandiflorum, via pattern differences and principal component analysis of their infrared spectra. Our results show that ginseng can be
distinguished from both sawdust and Platycodon grandiflorum, hence there is a potential of using infrared spectroscopy as a novel analytical technique in the authentication of ginseng. 相似文献
94.
Propranolol is a nonselective beta-blocker of the beta-adrenergic receptors, and the S-enantiomer is more active compared with the R-enantiomer. Clinically, it has been shown to be effective in hypermetabolic burn patients by decreasing cardiac work, protein catabolism, and lipolysis. While gene expression profiles have recently been reported in children receiving propranolol treatment, variations from one individual to another may have influenced the data analysis. Using iTRAQ-coupled 2D LC-MS/MS analysis, we report here the first study of protein profile in vascular smooth muscle cells incubated separately with the two enantiomers of propranolol. Four types of cellular proteins including metabolic enzymes, signaling molecules, cytoskeletal proteins, and those involved in DNA synthesis/protein translation displayed changes. The higher protein level of a number of enzymes involved in cellular anabolism and antioxidant activity in cells incubated with the S-enantiomer, as revealed by LC-MS/MS, was further supported by real-time PCR and Western blot analyses. Significantly, the increase in the anabolic activity associated with the higher level of metabolic enzymes was also supported by the higher intracellular concentration of the metabolic cofactor NAD+ which was a result of an increased oxidation of NADH. Our findings therefore provide molecular evidence on metabolic effect associated with propranolol treatment. The metabolic enzymes identified in our study may in turn be useful targets for future pharmaceutical interventions to reduce clinical side effects following propranolol treatment. 相似文献
95.
96.
Leifu Chang Xianwei Liu Yanbing Li Cui-Cui Liu Fan Yang Jindong Zhao Sen-Fang Sui 《Cell research》2015,25(6):726-737
Phycobilisomes (PBSs) are light-harvesting antennae that transfer energy to photosynthetic reaction centers in cyanobacteria and red algae. PBSs are supermolecular complexes composed of phycobiliproteins (PBPs) that bear chromophores for energy absorption and linker proteins. Although the structures of some individual components have been determined using crystallography, the three-dimensional structure of an entire PBS complex, which is critical for understanding the energy transfer mechanism, remains unknown. Here, we report the structures of an intact PBS and a PBS in complex with photosystem II (PSII) from Anabaena sp. strain PCC 7120 using single-particle electron microscopy in combination with biochemical and molecular analyses. In the PBS structure, all PBP trimers and the conserved linker protein domains were unambiguously located, and the global distribution of all chromophores was determined. We provide evidence that ApcE and ApcF are critical for the formation of a protrusion at the bottom of PBS, which plays an important role in mediating PBS interaction with PSII. Our results provide insights into the molecular architecture of an intact PBS at different assembly levels and provide the basis for understanding how the light energy absorbed by PBS is transferred to PSII. 相似文献
97.
98.
99.
利用ISSR分子标记技术对5个地区6个麦冬居群进行遗传多样性分析。选用10条扩增带型清晰且重复性好的引物进行扩增,共获得115条带,其中89条具有多态性,多态性比例为77.39%。当遗传相似系数(GS)为0.61时,可将6个麦冬居群分为2大类群。居群的GS平均值为0.643,表明供试居群之间存在较近的亲缘关系,且地域越近的其亲缘关系关系越近。研究表明ISSR分子标记技术能够很好地用于不同地域同种物种的亲缘关系分析。 相似文献
100.
An Yun Guo Kwok Sui Leung Parco Ming Fai Siu Jiang Hui Qin Simon Kwoon Ho Chow Ling Qin Chi Yu Li Wing Hoi Cheung 《Experimental Animals》2015,64(4):425-433
Sarcopenia is an age-related systemic syndrome with progressive deterioration in skeletal
muscle functions and loss in mass. Although the senescence-accelerated mouse P8 (SAMP8)
was reported valid for muscular ageing research, there was no report on the details such
as sarcopenia onset time. Therefore, this study was to investigate the change of muscle
mass, structure and functions during the development of sarcopenia. Besides the average
life span, muscle mass, structural and functional measurements were also studied. Male
SAMP8 animals were examined at month 6, 7, 8, 9, and 10, in which the right gastrocnemius
was isolated and tested for ex vivo contractile properties and fatigability while the
contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and typing
assessments. Results showed that the peak of muscle mass appeared at month 7 and the onset
of contractility decline was observed from month 8. Compared with month 8, most of the
functional parameters at month 10 decreased significantly. Structurally, muscle fiber type
IIA made up the largest proportion of the gastrocnemius, and the fiber size was found to
peak at month 8. Based on the altered muscle mass, structural and functional outcomes, it
was concluded that the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals
at month 8 should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is
confirmed that SAMP8 mouse can be used in sarcopenia research with established time line
in this study. 相似文献