全文获取类型
收费全文 | 151篇 |
免费 | 3篇 |
出版年
2021年 | 1篇 |
2019年 | 5篇 |
2018年 | 1篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 4篇 |
2014年 | 4篇 |
2013年 | 7篇 |
2012年 | 5篇 |
2011年 | 8篇 |
2010年 | 5篇 |
2009年 | 3篇 |
2008年 | 5篇 |
2007年 | 9篇 |
2006年 | 6篇 |
2005年 | 8篇 |
2004年 | 2篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2001年 | 1篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1992年 | 2篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1964年 | 2篇 |
排序方式: 共有154条查询结果,搜索用时 937 毫秒
71.
Zhao W Varghese M Yemul S Pan Y Cheng A Marano P Hassan S Vempati P Chen F Qian X Pasinetti GM 《Molecular neurodegeneration》2011,6(1):51-8
Background
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects spinal cord and cortical motor neurons. An increasing amount of evidence suggests that mitochondrial dysfunction contributes to motor neuron death in ALS. Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) is a principal regulator of mitochondrial biogenesis and oxidative metabolism.Results
In this study, we examined whether PGC-1α plays a protective role in ALS by using a double transgenic mouse model where PGC-1α is over-expressed in an SOD1 transgenic mouse (TgSOD1-G93A/PGC-1α). Our results indicate that PGC-1α significantly improves motor function and survival of SOD1-G93A mice. The behavioral improvements were accompanied by reduced blood glucose level and by protection of motor neuron loss, restoration of mitochondrial electron transport chain activities and inhibition of stress signaling in the spinal cord.Conclusion
Our results demonstrate that PGC-1α plays a beneficial role in a mouse model of ALS, suggesting that PGC-1α may be a potential therapeutic target for ALS therapy. 相似文献72.
Marano AV Gleason FH Bärlocher F Pires-Zottarelli CL Lilje O Schmidt SK Rasconi S Kagami M Barrera MD Sime-Ngando T Boussiba S de Souza JI Edwards JE 《Journal of microbiological methods》2012,89(1):22-32
Quantitative estimations of zoosporic fungi in the environment have historically received little attention, primarily due to methodological challenges and their complex life cycles. Conventional methods for quantitative analysis of zoosporic fungi to date have mainly relied on direct observation and baiting techniques, with subsequent fungal identification in the laboratory using morphological characteristics. Although these methods are still fundamentally useful, there has been an increasing preference for quantitative microscopic methods based on staining with fluorescent dyes, as well as the use of hybridization probes. More recently however PCR based methods for profiling and quantification (semi- and absolute) have proven to be rapid and accurate diagnostic tools for assessing zoosporic fungal assemblages in environmental samples. Further application of next generation sequencing technologies will however not only advance our quantitative understanding of zoosporic fungal ecology, but also their function through the analysis of their genomes and gene expression as resources and databases expand in the future. Nevertheless, it is still necessary to complement these molecular-based approaches with cultivation-based methods in order to gain a fuller quantitative understanding of the ecological and physiological roles of zoosporic fungi. 相似文献
73.
Carla GS Saad Ana CM Ribeiro Julio CB Moraes Liliam Takayama Celio R Goncalves Marcelo B Rodrigues Ricardo M de Oliveira Clovis A Silva Eloisa Bonfa Rosa MR Pereira 《Arthritis research & therapy》2012,14(5):R216
Introduction
Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy.Methods
Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients'' sclerostin levels, sclerostin binding low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls.Results
At baseline, AS patients had lower sclerostin levels (60.5 ± 32.7 vs. 96.7 ± 52.9 pmol/L, P = 0.002) and comparable sclerostin binding to LRP6 (P = 0.387) than controls. Improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (ASQoL) was observed at baseline vs. 6 vs. 12 months (P < 0.01). Concomitantly, a gradual increase in spine BMD (P < 0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r = 0.468, P < 0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P <0.01). Sclerostin levels progressively increased [baseline (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, P <0.001]. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls (72.7 ± 32.3 vs. 96.70 ± 52.85 pmol/L, P = 0.038). Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high C reactive protein (CRP) (≥ 5 mg/l) compared to the other 20 patients with normal CRP (P = 0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P = 0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values.Conclusions
Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy. 相似文献74.
Robert NG Miller David J Bertioli Franc C Baurens Candice MR Santos Paulo C Alves Natalia F Martins Roberto C Togawa Manoel T Souza Júnior Georgios J Pappas Júnior 《BMC plant biology》2008,8(1):15
Background
Many commercial banana varieties lack sources of resistance to pests and diseases, as a consequence of sterility and narrow genetic background. Fertile wild relatives, by contrast, possess greater variability and represent potential sources of disease resistance genes (R-genes). The largest known family of plant R-genes encode proteins with nucleotide-binding site (NBS) and C-terminal leucine-rich repeat (LRR) domains. Conserved motifs in such genes in diverse plant species offer a means for isolation of candidate genes in banana which may be involved in plant defence. 相似文献75.
76.
Soler AP Marano CW Bryans M Miller RD Garulacan LA Mauldin SK Stamato TD Mullin JM 《European journal of cell biology》1999,78(1):56-66
Tumor necrosis factor-alpha (TNF) induces apoptosis in confluent LLC-PK1 epithelial cells, but also activates NF-kappaB, a negative regulator of apoptosis. The presence of increased TNF-induced apoptosis causes a transient increase in epithelial permeability, but the epithelial barrier function recovers, as assessed by measuring the transepithelial electrical resistance, the paracellular flux of mannitol and by the electron microscopic evaluation of the penetration of the electron-dense dye ruthenium red across the tight junctions. The integrity of the epithelial cell layer is maintained by rearrangement of non-apoptotic cells in the monolayer and by the phagocytosis of apoptotic fragments. To study the role of NF-kappaB in an epithelium exposed to TNF, NF-kappaB was inhibited in LLC-PK1 epithelial cells with either the dietary compound, curcumin, or by transfection with a dominant negative mutant inhibitor I kappaB alpha. Replacement of serine 32 and 36 by alanine has been shown to prevent its phosphorylation and degradation, blocking NF-kappaB activation. Inhibition of NF-kappaB altered the morphology of TNF-induced apoptotic cells, which showed lack of fragmentation and membrane blebbings, and absence of phagocytosis by neighboring cells. TNF treatment of NF-kappaB-inhibited cells also caused altered distribution of the tight junction-associated protein ZO-1, increased epithelial leakiness, and impaired the recovery of the epithelial barrier function, which normally occurs 6 hours after TNF treatment of LLC-PK1 cells. These data demonstrate that NF-kappaB activation is required for the maintenance of the barrier function of an epithelium undergoing TNF-induced apoptosis. 相似文献
77.
78.
Prinetti A Marano N Prioni S Chigorno V Mauri L Casellato R Tettamanti G Sonnino S 《Glycoconjugate journal》2000,17(3 -4):223-232
Src family kinases play a relevant role in the development and differentiation of neuronal cells. They are abundant in sphingolipid-enriched membrane domains of many cell types, and these domains are hypothesized to function in bringing together molecules important to signal transduction. We studied the association of Src family tyrosine kinases and their negative regulatory kinase, Csk, with sphingolipids in sphingolipid-enriched domains of rat cerebellar granule cells differentiated in culture. We find that c-Src, Lyn and Csk are enriched in the sphingolipid-enriched fraction prepared from these cells. Coimmunoprecipitation experiments show that these and sphingolipids are part of the same domain. Cross-linking experiments with a photoactivable, radioactive GD1b derivative show that c-Src and Lyn, which are anchored to the membrane via a myristoyl chain, associate directly with GD1b. Csk, which is not inserted in the hydrophobic core of the membrane, is not photolabeled by this ganglioside. These results suggest that lipid-lipid, lipid-protein, and protein-protein interactions cooperate to maintain domain structure. We hypothesize that such interactions might play a role in the process of neuronal differentiation. 相似文献
79.
Ankit Magotra I. D. Gupta Archana Verma Rani Alex Vineeth MR Tavsief Ahmad 《Animal biotechnology》2019,30(1):75-81
The present study was conducted to identify polymorphisms in CACNA2D1 gene and their association with clinical mastitis and production traits. Exon 18 and its flanking regions were screened for the presence of SNPs. Statistical analysis was performed to identify association of period of birth, breed, and genotype with mastitis incidence on randomly selected 103 Sahiwal and 102 Karan Fries cattle. PCR-RFLP analysis revealed that g.38819398G?>?A mutation in exon 18 (269?bp amplicon) of CACNA2D1 gene resolved into AA, AG, and GG genotypes in Sahiwal and Karan Fries cattle. Wald chi-square analysis revealed that the period of birth, breed, and genotype were significantly associated with mastitis incidence. GG genotyped cattle were found to be less susceptible to mastitis. Least square analysis revealed that GG and AG genotype animals of G38819398A SNP of CACNA2D1 gene in Sahiwal as well as in Karan Fries cattle were associated with higher average milk yields during 1st, 2nd, and 3rd lactations (P?<?0.01). These observations and their differential association with the incidence of mastitis and production traits can be utilized as an aid to selection for simultaneous improvement of both antagonistic traits; however, validation of results on large number of animals is warranted. 相似文献
80.
Daniele Aureli Antonio Contardi Biagio Giaccio Brian Jicha Cristina Lemorini Sergio Madonna Donatella Magri Federica Marano Salvatore Milli Valerio Modesti Maria Rita Palombo Roxane Rocca 《PloS one》2015,10(4)
The Ficoncella site in northern Latium (Italy) represents a unique opportunity to investigate the modalities of a short occupation in an alluvial setting during the Lower Palaeolithic. The small excavation area yielded a lithic assemblage, a carcass of Palaeoloxodon antiquus, and some other faunal remains. The main objectives of the study are to better characterize the depositional context where the Palaeoloxodon and the lithic assemblage occur, and to evaluate with greater precision the occupation dynamics. A 25 m-long well was drilled just above the top of the terrace of the Ficoncella site and faunal and lithic remains were analyzed with current and innovative techniques. The archaeological site contains floodplain deposits as it is located next to a small incised valley that feeds into a larger valley of the Mignone River. A tephra layer capping the site is 40Ar/39Ar dated to 441± 8 ka. Collectively, the geochronologic, tephrochronologic and geologic data, suggest the site was occupied during MIS 13. The new results should prompt further research at Ficoncella in order to improve our understanding of the dynamics of human settlement in Europe during the Early to Middle Pleistocene. 相似文献