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151.
Corona C Frazzini V Silvestri E Lattanzio R La Sorda R Piantelli M Canzoniero LM Ciavardelli D Rizzarelli E Sensi SL 《PloS one》2011,6(3):e17971
Background
The pathogenic road map leading to Alzheimer''s disease (AD) is still not completely understood; however, a large body of studies in the last few years supports the idea that beside the classic hallmarks of the disease, namely the accumulation of amyloid-β (Aβ) and neurofibrillary tangles, other factors significantly contribute to the initiation and the progression of the disease. Among them, mitochondria failure, an unbalanced neuronal redox state, and the dyshomeostasis of endogenous metals like copper, iron, and zinc have all been reported to play an important role in exacerbating AD pathology. Given these factors, the endogenous peptide carnosine may be potentially beneficial in the treatment of AD because of its free-radical scavenger and metal chelating properties.Methodology
In this study, we explored the effect of L-carnosine supplementation in the 3xTg-AD mouse, an animal model of AD that shows both Aβ- and tau-dependent pathology.Principal Findings
We found that carnosine supplementation in 3xTg-AD mice promotes a strong reduction in the hippocampal intraneuronal accumulation of Aβ and completely rescues AD and aging-related mitochondrial dysfunctions. No effects were found on tau pathology and we only observed a trend toward the amelioration of cognitive deficits.Conclusions and Significance
Our data indicate that carnosine can be part of a combined therapeutic approach for the treatment of AD. 相似文献152.
The movement of water accompanying solutes between the cytoplasm and the mitochondrial spaces is central for mitochondrial volume homeostasis, an important function for mitochondrial activities and for preventing the deleterious effects of excess matrix swelling or contraction. While the discovery of aquaporin water channels in the inner mitochondrial membrane provided valuable insights into the basis of mitochondrial plasticity, questions regarding the identity of mitochondrial water permeability and its regulatory mechanism remain open. Here, we use a stopped flow light scattering approach to define the water permeability and Arrhenius activation energy of the rat liver whole intact mitochondrion and its membrane subcompartments. The water permeabilities of whole brain and testis mitochondria as well as liposome models of the lipid bilayer composing the liver inner mitochondrial membrane are also characterized. Besides finding remarkably high water permeabilities for both mitochondria and their membrane subcompartments, the existence of additional pathways of water movement other than aquaporins are suggested. 相似文献
153.
Domenico Carputo 《Sexual plant reproduction》1999,12(1):27-31
Crosses between triploid and diploid genotypes are usually the best sources of trisomics in potato as well as in several
other crop species. However, 3×× 2× crosses between triploid (2n=3×=36; 2EBN) Solanum commersonii-S. tuberosum hybrids and diploid (2n= 2×=24; 2EBN) genotypes gave progenies with a high number of extra chromosomes, 29–36, suggesting
that only eggs with 17–24 chromosomes produced embryos that reached full development. Our hypothesis is that although triploids
produce eggs with a range of chromosome numbers, 3×× 2× crosses involving a 2×(2EBN) parent favor eggs with a high chromosome
number. These eggs have higher probabilities of possessing the same endosperm balance number (EBN) value (i.e. 1) of gametes
produced by the 2EBN diploid parent to give the required 2:1 maternal to paternal EBN ratio in the hybrid endosperm. Under
this model, trisomics are produced only if the diploid parent has an EBN of 1. Based on our results and those reported in
the literature, it is proposed that in 3×(2EBN) × 2×(2EBN) crosses the endosperm balance number exercises negative selection
for gametes with a low chromosome number, and a corresponding low EBN, and positive selection for gametes with a high chromosome
number and EBN.
Received: 2 April 1998 / Revision accepted: 27 October 1998 相似文献
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Loss of ATM kinase, a transducer of the DNA damage response and redox sensor, causes the neurodegenerative disorder ataxia-telangiectasia (A-T). While a great deal of progress has been made in elucidating the ATM-dependent DNA damage response (DDR) network, a key challenge remains in understanding the selective susceptibility of the nervous system to faulty DDR. Several factors appear implicated in the neurodegenerative phenotype in A-T, but which of them plays a crucial role remains unclear, especially since mouse models of A-T do not fully mirror the respective human syndrome. Therefore, a number of human neural stem cell (hNSC) systems have been developed to get an insight into the molecular mechanisms of neurodegeneration as consequence of ATM inactivation. Here we review the hNSC systems developed by us an others to model A-T. 相似文献
157.
Lago Jennifer L. Burcar Bradley T. Hud Nicholas V. Febrian Rio Mehta Christopher Bracher Paul J. Atlas Zachary D. Pasek Matthew A. 《Origins of life and evolution of the biosphere》2020,50(1-2):1-14
Origins of Life and Evolution of Biospheres - The numerous and varied roles of phosphorylated organic molecules in biochemistry suggest they may have been important to the origin of life. The... 相似文献
158.
Daniela Valenti Domenico De Rasmo Anna Signorile Leonardo Rossi Lidia de Bari Iris Scala Barbara Granese Sergio Papa Rosa Anna Vacca 《生物化学与生物物理学报:疾病的分子基础》2013,1832(4):542-552
A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria. In this study we have tested the potential of epigallocatechin-3-gallate (EGCG) – a natural polyphenol component of green tea – to counteract the mitochondrial energy deficit found in DS cells. We found that EGCG, incubated with cultured lymphoblasts and fibroblasts from DS subjects, rescued mitochondrial complex I and ATP synthase catalytic activities, restored oxidative phosphorylation efficiency and counteracted oxidative stress. These effects were associated with EGCG-induced promotion of PKA activity, related to increased cellular levels of cAMP and PKA-dependent phosphorylation of the NDUFS4 subunit of complex I. In addition, EGCG strongly promoted mitochondrial biogenesis in DS cells, as associated with increase in Sirt1-dependent PGC-1α deacetylation, NRF-1 and T-FAM protein levels and mitochondrial DNA content.In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS. 相似文献
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160.
Metodi?D. Metodiev Kyle Thompson Charlotte?L. Alston Andrew?A.M. Morris Langping He Zarah Assouline Marlène Rio Nadia Bahi-Buisson Angela Pyle Helen Griffin Stefan Siira Aleksandra Filipovska Arnold Munnich Patrick?F. Chinnery Robert McFarland Agnès R?tig Robert?W. Taylor 《American journal of human genetics》2016,99(1):246