全文获取类型
收费全文 | 124篇 |
免费 | 16篇 |
出版年
2022年 | 1篇 |
2021年 | 5篇 |
2020年 | 6篇 |
2019年 | 9篇 |
2018年 | 5篇 |
2017年 | 4篇 |
2016年 | 9篇 |
2015年 | 11篇 |
2014年 | 5篇 |
2013年 | 3篇 |
2012年 | 6篇 |
2011年 | 5篇 |
2010年 | 7篇 |
2009年 | 4篇 |
2008年 | 4篇 |
2007年 | 3篇 |
2006年 | 7篇 |
2005年 | 5篇 |
2004年 | 2篇 |
2003年 | 1篇 |
2002年 | 3篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 7篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1989年 | 4篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1964年 | 4篇 |
排序方式: 共有140条查询结果,搜索用时 984 毫秒
131.
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
132.
133.
The mutation rates of di-, tri- and tetranucleotide repeats in Drosophila melanogaster 总被引:3,自引:1,他引:3
Schug MD; Hutter CM; Wetterstrand KA; Gaudette MS; Mackay TF; Aquadro CF 《Molecular biology and evolution》1998,15(12):1751-1760
In a recent study, we reported that the combined average mutation rate of
10 di-, 6 tri-, and 8 tetranucleotide repeats in Drosophila melanogaster
was 6.3 x 10(-6) mutations per locus per generation, a rate substantially
below that of microsatellite repeat units in mammals studied to date (range
= 10(-2)-10(-5) per locus per generation). To obtain a more precise
estimate of mutation rate for dinucleotide repeat motifs alone, we assayed
39 new dinucleotide repeat microsatellite loci in the mutation accumulation
lines from our earlier study. Our estimate of mutation rate for a total of
49 dinucleotide repeats is 9.3 x 10(-6) per locus per generation, only
slightly higher than the estimate from our earlier study. We also estimated
the relative difference in microsatellite mutation rate among di-, tri-,
and tetranucleotide repeats in the genome of D. melanogaster using a method
based on population variation, and we found that tri- and tetranucleotide
repeats mutate at rates 6.4 and 8.4 times slower than that of dinucleotide
repeats, respectively. The slower mutation rates of tri- and
tetranucleotide repeats appear to be associated with a relatively short
repeat unit length of these repeat motifs in the genome of D. melanogaster.
A positive correlation between repeat unit length and allelic variation
suggests that mutation rate increases as the repeat unit lengths of
microsatellites increase.
相似文献
134.
Model selection is an essential issue in longitudinal data analysis since many different models have been proposed to fit the covariance structure. The likelihood criterion is commonly used and allows to compare the fit of alternative models. Its value does not reflect, however, the potential improvement that can still be reached in fitting the data unless a reference model with the actual covariance structure is available. The score test approach does not require the knowledge of a reference model, and the score statistic has a meaningful interpretation in itself as a goodness-of-fit measure. The aim of this paper was to show how the score statistic may be separated into the genetic and environmental parts, which is difficult with the likelihood criterion, and how it can be used to check parametric assumptions made on variance and correlation parameters. Selection of models for genetic analysis was applied to a dairy cattle example for milk production. 相似文献
135.
It is of interest to compile available information on the root canal morphology of primary maxillary molars from known literature. The literature resources used to collect data include Medline/PubMed, The Cochrane Central Register of Clinical Trials, SIGLE and Science Direct. Data consists of type of population, number of teeth per study, number of root canals, canal length and type of root canal configuration. We used data from a total of 13 studies (951 primary maxillary molars). Maxillary molars (1st and 2nd) are dominant for two roots variant. The first molar the mean root length ranges from 7.9mm - 8.1mm. The second molar ranges from 7.2mm-8.5mm. Type I (explain in a phrase) canal morphology is the common variant in both the molars. Data shows that Root Canal morphology shows variations with the diagnostic aid (example micro CT) used and in different ethnic populations. 相似文献
136.
J. Kalervo Hiltunen Kaija J. Autio Melissa S. Schonauer V.A. Samuli Kursu Carol L. Dieckmann Alexander J. Kastaniotis 《BBA》2010,1797(6-7):1195-1202
Recent studies have revealed that mitochondria are able to synthesize fatty acids in a malonyl-CoA/acyl carrier protein (ACP)-dependent manner. This pathway resembles bacterial fatty acid synthesis (FAS) type II, which uses discrete, nuclearly encoded proteins. Experimental evidence, obtained mainly through using yeast as a model system, indicates that this pathway is essential for mitochondrial respiratory function. Curiously, the deficiency in mitochondrial FAS cannot be complemented by inclusion of fatty acids in the culture medium or by products of the cytosolic FAS complex. Defects in mitochondrial FAS in yeast result in the inability to grow on nonfermentable carbon sources, the loss of mitochondrial cytochromes a/a3 and b, mitochondrial RNA processing defects, and loss of cellular lipoic acid. Eukaryotic FAS II generates octanoyl-ACP, a substrate for mitochondrial lipoic acid synthase. Endogenous lipoic acid synthesis challenges the hypothesis that lipoic acid can be provided as an exogenously supplied vitamin. Purified eukaryotic FAS II enzymes are catalytically active in vitro using substrates with an acyl chain length of up to 16 carbon atoms. However, with the exception of 3-hydroxymyristoyl-ACP, a component of respiratory complex I in higher eukaryotes, the fate of long-chain fatty acids synthesized by the mitochondrial FAS pathway remains an enigma. The linkage of FAS II genes to published animal models for human disease supports the hypothesis that mitochondrial FAS dysfunction leads to the development of disorders in mammals. 相似文献
137.
Parker M. Pennington PhD Kira L. Marshall MS Jonnie M. Capiro MS Lauren Howard DVM Barbara S. Durrant PhD 《Zoo biology》2020,39(2):141-144
All extant species in the Rhinocerotidae family are experiencing escalating threats in the wild, making self-sustaining captive populations essential genetic reservoirs for species survival. Assisted reproductive technologies (ARTs) will become increasingly important for achieving and maintaining ex situ population sustainability and genetic diversity. Previous reports have shown that a large proportion of captive southern white rhinoceros (SWR) females are irregularly cyclic or acyclic, and that cycling females display two different estrous cycle lengths of approximately 30 or 70 days. It has been suggested that the longer estrous cycle length is infertile or subfertile, as no term pregnancies have been observed following long cycles. Here we report the achievement of two pregnancies following long luteal phases, using ovulation induction and artificial insemination with either fresh or frozen-thawed semen. One female SWR conceived on the first insemination attempt and gave birth to a live offspring. A second female conceived twice in consecutive long cycles although the first embryo was resorbed by 33 days post-insemination. A pregnancy from this female's second insemination is ongoing with expected parturition in November 2019. Whether prolonged estrous cycles in SWR are subfertile or infertile in natural breeding situations remains unclear. However, our findings demonstrate that the application of ARTs following prolonged cycles can result the successful establishment of pregnancies in SWR. Therefore, with ARTs, female SWR otherwise considered nonreproductive due to long estrous cycles may still have the potential for representation and contribution to the ex situ population. 相似文献
138.
Yan Chao Cui Yu Sheng Qiu Qiong Wu Gang Bu Amira Peli Seoh Wei Teh Kok Pian Ang Narcisse MS Joseph Avin Ee-Hwan Koh Aisha Farhana Badr Alzahrani Mohammed Safwan Ali Khan Antony V Samrot Pooi Ling Mok Suresh Kumar Subbiah 《Experimental biology and medicine (Maywood, N.J.)》2021,246(10):1177
Osteoblasts play an important role in bone regeneration and repair. The hypoxia condition in bone occurs when bone undergoes fracture, and this will trigger a series of biochemical and mechanical changes to enable bone repair. Hence, it is interesting to observe the metabolites and metabolism changes when osteoblasts are exposed to hypoxic condition. This study has looked into the response of human osteoblast hFOB 1.19 under normoxic and hypoxic conditions by observing the cell growth and utilization of metabolites via Phenotype MicroArrays™ under these two different oxygen concentrations. The cell growth of hFOB 1.19 under hypoxic condition showed better growth compared to hFOB 1.19 under normal condition. In this study, osteoblast used glycolysis as the main pathway to produce energy as hFOB 1.19 in both hypoxic and normoxic conditions showed cell growth in well containing dextrin, glycogen, maltotriose, D-maltose, D-glucose-6-phospate, D-glucose, D-mannose, D-Turanose, D-fructose-6-phosphate, D-galactose, uridine, adenosine, inosine and α-keto-glutaric acid. In hypoxia, the cells have utilized additional metabolites such as α-D-glucose-1-phosphate and D-fructose, indicating possible activation of glycogen synthesis and glycogenolysis to metabolize α-D-glucose-1-phosphate. Meanwhile, during normoxia, D-L-α-glycerol phosphate was used, and this implies that the osteoblast may use glycerol-3-phosphate shuttle and oxidative phosphorylation to metabolize glycerol-3-phosphate. 相似文献
139.
140.
MS Nandhu Jes Paul Korah P Kuruvilla Anitha Malat Chinthu Romeo CS Paulose 《Journal of biomedical science》2011,18(1):5
Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine
depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia
is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested
to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric
acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine
induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed
a significant increase in Bmax (P < 0.001) in the cerebral cortex of 6-hydroxydopamine infused rat compared to control. Real Time PCR amplification of NMDA2B,
mGluR5, bax, and ubiquitin carboxy-terminal hydrolase were up regulated in cerebral cortex of 6-hydroxydopamine infused rats
compared to control. Gene expression studies of GLAST, ά-Synuclien and Cyclic AMP response element-binding protein showed
a significant (P < 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out
to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal
of glutamate receptors and behaviour abnormality shown in the Parkinson's rat model. The therapeutic significance in Parkinson's
disease is of prominence. 相似文献