全文获取类型
收费全文 | 351篇 |
免费 | 53篇 |
国内免费 | 1篇 |
出版年
2024年 | 1篇 |
2022年 | 5篇 |
2021年 | 15篇 |
2020年 | 20篇 |
2019年 | 26篇 |
2018年 | 20篇 |
2017年 | 15篇 |
2016年 | 19篇 |
2015年 | 26篇 |
2014年 | 24篇 |
2013年 | 20篇 |
2012年 | 26篇 |
2011年 | 16篇 |
2010年 | 10篇 |
2009年 | 10篇 |
2008年 | 11篇 |
2007年 | 22篇 |
2006年 | 22篇 |
2005年 | 19篇 |
2004年 | 12篇 |
2003年 | 11篇 |
2002年 | 7篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 9篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1989年 | 4篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有405条查询结果,搜索用时 15 毫秒
351.
Valentín Cóppola-Segovia Clarissa Cavarsan Flavia G Maia Anete C Ferraz Lia S Nakao Marcelo MS Lima Silvio M Zanata 《Molecular neurobiology》2017,54(8):5798-5806
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons of the substantia nigra pars compacta (SNpc), leading to the major clinical abnormalities that characterize this disease. Although PD’s etiology is unknown, α-synuclein aggregation plays a pivotal role in PD pathogenesis, which could be associated to some pathological processes such as oxidative stress, endoplasmic reticulum (ER) stress, impaired protein degradation, and mitochondrial dysfunction. Increasing experimental evidence indicates that ER stress is involved in PD, however most of the described results employed cultured cell lines and genetically modified animal models. In this study, we developed a new ER stress rat model employing the well-known ER stressor tunicamycin (Tm). To evaluate if ER stress was able to induce PD features, we performed an intranigral injection of Tm (0.1 μg/cerebral hemisphere) and animals (male Wistar rats) were analyzed 7 days post injection. The classical 6-OHDA neurotoxin model (1 μg/cerebral hemisphere) was used as an established positive control for PD. We show that Tm injection induced locomotor impairment, dopaminergic neurons death, and activation of astroglia. In addition, we observed an extensive α-synuclein oligomerization in SNpc of Tm-injected animals when compared with DMSO-injected controls. Finally, both Tm and 6-OHDA treated animals presented increased levels of ER stress markers. Taken together, these findings show for the first time that the ER stressor Tm recapitulates some of the phenotypic characteristics observed in rodent models of PD, reinforcing the concept that ER stress could be an important contributor to the pathophysiology of PD. Therefore, we propose the intranigral Tm injection as a new ER stress-based model for the study of PD in vivo. 相似文献
352.
Chemical Variability,Antioxidant and Antifungal Activities of Essential Oils and Hydrosol Extract of Calendula arvensis L. from Western Algeria
下载免费PDF全文
![点击此处可从《化学与生物多样性》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Rania Belabbes Mohammed El Amine Dib Nassim Djabou Faiza Ilias Boufeldja Tabti Jean Costa Alain Muselli 《化学与生物多样性》2017,14(5)
The chemical composition of the essential oils and hydrosol extract from aerial parts of Calendula arvensis L. was investigated using GC‐FID and GC/MS. Intra‐species variations of the chemical compositions of essential oils from 18 Algerian sample locations were investigated using statistical analysis. Chemical analysis allowed the identification of 53 compounds amounting to 92.3 – 98.5% with yields varied of 0.09 – 0.36% and the main compounds were zingiberenol 1 (8.7 – 29.8%), eremoligenol (4.2 – 12.5%), β‐curcumene (2.1 – 12.5%), zingiberenol 2 (4.6 – 19.8%) and (E,Z)‐farnesol (3.5 – 23.4%). The study of the chemical variability of essential oils allowed the discrimination of two main clusters confirming that there is a relation between the essential oil compositions and the harvest locations. Different concentrations of essential oil and hydrosol extract were prepared and their antioxidant activity were assessed using three methods (2,2‐diphenyl‐1‐picrylhydrazyl, Ferric‐Reducing Antioxidant Power Assay and β‐carotene). The results showed that hydrosol extract presented an interesting antioxidant activity. The in vitro antifungal activity of hydrosol extract produced the best antifungal inhibition against Penicillium expansum and Aspergillus niger, while, essential oil was inhibitory at relatively higher concentrations. Results showed that the treatments of pear fruits with essential oil and hydrosol extract presented a very interesting protective activity on disease severity of pears caused by P. expansum. 相似文献
353.
Metal‐Ion Batteries: Open‐Structured V2O5·nH2O Nanoflakes as Highly Reversible Cathode Material for Monovalent and Multivalent Intercalation Batteries (Adv. Energy Mater. 14/2017)
下载免费PDF全文
![点击此处可从《Liver Transplantation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
354.
Alternative splicing and protein function 总被引:1,自引:0,他引:1
AD?Neverov II?Artamonova RN?Nurtdinov D?Frishman MS?GelfandEmail author AA?Mironov 《BMC bioinformatics》2005,6(1):266
Background
Alternative splicing is a major mechanism of generating protein diversity in higher eukaryotes. Although at least half, and probably more, of mammalian genes are alternatively spliced, it was not clear, whether the frequency of alternative splicing is the same in different functional categories. The problem is obscured by uneven coverage of genes by ESTs and a large number of artifacts in the EST data. 相似文献355.
The tetraspanin CD81 is induced in the mesolimbic dopaminergic pathway after cocaine administration. To further investigate its role, a regulatable lentivirus (Lenti-CD81) bearing the CD81 gene under the control of a tetracycline-inducible promoter and lentiviruses expressing short hairpin RNA (shRNA) targeted against CD81 (Lenti-CD81-shRNAs) have been prepared. Infection of HEK293T cells in vitro with Lenti-CD81-shRNAs resulted in 96.5% gene silencing (from quantitative real-time PCR(qRT-PCR) and immunocytochemistry). In vivo delivery of Lenti-CD81-shRNA into the nucleus accumbens or ventral tegmental area resulted in 91.3 and 94% silencing of endogenous CD81, respectively. Stereotaxic injection of Lenti-CD81 into these regions, resulting in CD81 overexpression, induced a four- to fivefold increase in locomotor activity after chronic cocaine administration, which returned to basal levels when Lenti-CD81-shRNA had been coinjected or when CD81 expression was blocked by doxycycline. Furthermore, silencing endogenous CD81 in vivo resulted in a significant decrease in locomotor activity over controls, again suppressing cocaine-induced behaviour. 相似文献
356.
Opposite role of yeast ING family members in p53-dependent transcriptional activation 总被引:8,自引:0,他引:8
Nourani A Howe L Pray-Grant MG Workman JL Grant PA Côté J 《The Journal of biological chemistry》2003,278(21):19171-19175
357.
Metabolic engineering has been defined as a directed improvement of product formation or cellular properties by modification of specific biochemical pathways or introduction of new enzymatic reactions by recombinant DNA technology. The use of metabolic flux analysis (MFA) has helped in the understanding of the key limitation in the metabolic pathways of cultured animal cells. The MFA of the major nutrients glucose and glutamine showed that the flux of glucose to the TCA cycle and its subsequent utilization is limited as a result of the lack of certain key enzymes in the pathway. One of the key enzymes controlling this flux is pyruvate carboxylase. Introduction of this enzyme into mammalian cells has been shown to improve the utilization of glucose and limit the production of lactate and ammonia, which are deleterious to cell growth. In the present work a yeast pyruvate carboxylase gene has been introduced into mammalian (HEK 293) and insect (Trichoplusia ni High-Five) cells, resulting in the cytosolic expression of the enzyme. In both cases the resulting transfected cells were able to utilize glucose and glutamine more efficiently and produce lower amounts of lactate and ammonia. Differences in the amino acid utilization pattern were also observed, indicating changes in the basic metabolism of the cells. The performance of the transfected cells as expression systems for adenovirus and baculovirus vectors, respectively, has also been examined. The results obtained and their impact on the process development for protein and viral vector production are discussed. 相似文献
358.
One of the major limitations in the production of adenoviral vectors is the reduction in cell-specific productivity observed for increasing cell density at infection in batch cultures. This observation strongly suggests some nutrient depletion and/or metabolite inhibition in the media. These limitations have been partially overcome through other feeding strategies, such as fed-batch and sequential batch operations. To improve these results, we evaluated perfusion as a strategy to increase the volumetric productivity of HEK-293 cell cultures, by allowing productive infection at higher cell densities. An acoustic cell separator was employed in consideration of the increased shear sensitivity of the cells during the infection phase. The effects of perfusion rate and cell density at infection on the production of a recombinant adenovirus expressing the GFP were investigated. The perfusion mode allowed successful infection at cell densities in the range of 2.4-3 x 10(6) cell/mL, while maintaining a similar cell specific productivity (17,900 +/- 2400 VP/cell) to that of a batch infected at a low cell density (5 x 10(5) cell/mL). The highest virus concentrations (4.1 +/- 0.6 x 10(10) VP/mL) were attained for a feed rate of 2 vol/d and constituted a fivefold increase compared to a batch with medium replacement. Rapid assessment of the infection status was achieved through the use of on-line monitoring of respiration, fluorescence, and biovolume. Analysis of the kinetics of nutrient consumption and metabolite production revealed that a reduction in specific productivity is correlated with reduced metabolic activity. 相似文献
359.
360.
Angélica MS Firmo Mônica MP Tognella Saulo R Silva Raynner RRD Barboza Rômulo RN Alves 《Journal of ethnobiology and ethnomedicine》2012,8(1):1-12