全文获取类型
收费全文 | 17655篇 |
免费 | 1642篇 |
国内免费 | 1530篇 |
出版年
2024年 | 20篇 |
2023年 | 228篇 |
2022年 | 252篇 |
2021年 | 837篇 |
2020年 | 600篇 |
2019年 | 777篇 |
2018年 | 660篇 |
2017年 | 509篇 |
2016年 | 781篇 |
2015年 | 1173篇 |
2014年 | 1281篇 |
2013年 | 1472篇 |
2012年 | 1659篇 |
2011年 | 1481篇 |
2010年 | 906篇 |
2009年 | 782篇 |
2008年 | 1037篇 |
2007年 | 796篇 |
2006年 | 770篇 |
2005年 | 606篇 |
2004年 | 531篇 |
2003年 | 461篇 |
2002年 | 397篇 |
2001年 | 345篇 |
2000年 | 275篇 |
1999年 | 270篇 |
1998年 | 187篇 |
1997年 | 163篇 |
1996年 | 156篇 |
1995年 | 149篇 |
1994年 | 137篇 |
1993年 | 118篇 |
1992年 | 156篇 |
1991年 | 133篇 |
1990年 | 101篇 |
1989年 | 106篇 |
1988年 | 66篇 |
1987年 | 55篇 |
1986年 | 65篇 |
1985年 | 70篇 |
1984年 | 25篇 |
1983年 | 27篇 |
1982年 | 30篇 |
1981年 | 12篇 |
1980年 | 26篇 |
1979年 | 21篇 |
1978年 | 16篇 |
1977年 | 19篇 |
1974年 | 9篇 |
1972年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
2.
3.
<正>Research concerning senescence has become a hotspot since the conception of‘cellular senescence’was put forward by Drs.Hayflick and Moorhead over five decades ago[1].Recently,a paper published in Science by Kang and colleagues,which this article aims to comment on,provides evidence of a new pathway involved in senescence[2].Senescence is a physiological and pathological process induced by numerous factors,during which cell growth ceases 相似文献
4.
5.
Mitchell P Rosen A Musa Zamah Shehua Shen Anthony T Dobson Charles E McCulloch Paolo F Rinaudo Julie D Lamb Marcelle I Cedars 《Reproductive biology and endocrinology : RB&E》2009,7(1):35-8
Background
Ovarian stimulation for assisted reproductive technology (ART) overcomes the physiologic process to develop a single dominant follicle. However, following stimulation, egg recovery rates are not 100%. The objective of this study is to determine if the follicular fluid hormonal environment is associated with oocyte recovery. 相似文献6.
Metabolic homeostasis is critical for all biological processes in the brain. The metabolites are considered the best indicators of cell states and their rapid fluxes are extremely sensitive to cellular changes. While there are a few studies on the metabolomics of Parkinson’s disease, it lacks longitudinal studies of the brain metabolic pathways affected by aging and the disease. Using ultra-high performance liquid chromatography and tandem mass spectroscopy (UPLC/MS), we generated the metabolomics profiling data from the brains of young and aged male PD-related α-synuclein A53T transgenic mice as well as the age- and gender-matched non-transgenic (nTg) controls. Principal component and unsupervised hierarchical clustering analyses identified distinctive metabolites influenced by aging and the A53T mutation. The following metabolite set enrichment classification revealed the alanine metabolism, redox and acetyl-CoA biosynthesis pathways were substantially disturbed in the aged mouse brains regardless of the genotypes, suggesting that aging plays a more prominent role in the alterations of brain metabolism. Further examination showed that the interaction effect of aging and genotype only disturbed the guanosine levels. The young A53T mice exhibited lower levels of guanosine compared to the age-matched nTg controls. The guanosine levels remained constant between the young and aged nTg mice, whereas the aged A53T mice showed substantially increased guanosine levels compared to the young mutant ones. In light of the neuroprotective function of guanosine, our findings suggest that the increase of guanosine metabolism in aged A53T mice likely represents a protective mechanism against neurodegeneration, while monitoring guanosine levels could be applicable to the early diagnosis of the disease. 相似文献
7.
In the developing central nervous system (CNS), progenitor cells differentiate into progeny to form functional neural circuits. Radial glial cells (RGs) are a transient progenitor cell type that is present during neurogenesis. It is thought that a combination of neural trophic factors, neurotransmitters and electrical activity regulates the proliferation and differentiation of RGs. However, it is less clear how epigenetic modulation changes RG proliferation. We sought to explore the effect of histone deacetylase (HDAC) activity on the proliferation of RGs in the visual optic tectum of Xenopus laevis. We found that the number of BrdU-labeled precursor cells along the ventricular layer of the tectum decrease developmentally from stage 46 to stage 49. The co-labeling of BrdU-positive cells with brain lipid-binding protein (BLBP), a radial glia marker, showed that the majority of BrdU-labeled cells along the tectal midline are RGs. BLBP-positive cells are also developmentally decreased with the maturation of the brain. Furthermore, HDAC1 expression is developmentally down-regulated in tectal cells, especially in the ventricular layer of the tectum. Pharmacological blockade of HDACs using Trichostatin A (TSA) or Valproic acid (VPA) decreased the number of BrdU-positive, BLBP-positive and co-labeling cells. Specific knockdown of HDAC1 by a morpholino (HDAC1-MO) decreased the number of BrdU- and BLBP-labeled cells and increased the acetylation level of histone H4 at lysine 12 (H4K12). The visual deprivation-induced increase in BrdU- and BLBP-positive cells was blocked by HDAC1 knockdown at stage 49 tadpoles. These data demonstrate that HDAC1 regulates radial glia cell proliferation in the developing optical tectum of Xenopus laevis. 相似文献
8.
9.
Yao Shen Yueyang Tian Xiaojie Shi Jianbo Yang Li Ouyang Jieqiong Gao Jianxin Lu 《Cell biochemistry and function》2014,32(6):530-537
Astrocytes play a key role in removing the synaptically released glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. However, high concentration of glutamate leads to toxicity in astrocytes, and the underlying mechanisms are unclear. The purpose of this study was to investigate whether energy metabolism disorder, especially impairment of mitochondrial respiration, is involved in the glutamate‐induced gliotoxicity. Exposure to 10‐mM glutamate for 48 h stimulated glycolysis and respiration in astrocytes. However, the increased oxygen consumption was used for proton leak and non‐mitochondrial respiration, but not for oxidative phosphorylation and ATP generation. When the exposure time extended to 72 h, glycolysis was still activated for ATP generation, but the mitochondrial ATP‐linked respiration of astrocytes was reduced. The glutamate‐induced astrocyte damage can be mimicked by the non‐metabolized substrate d ‐aspartate but reversed by the non‐selective glutamate transporter inhibitor TBOA. In addition, the glutamate toxicity can be partially reversed by vitamin E. These findings demonstrate that changes of bioenergetic profile occur in cultured cortical astrocytes exposed to high concentration of glutamate and highlight the role of mitochondria respiration in glutamate‐induced gliotoxicity in cortical astrocytes. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
10.
We determined the best extraction buffer for proteomic investigation using formalin-fixation and paraffin-embedded (FFPE) specimens. A Zwittergent 3–16 based buffer, sodium dodecyl sulfate (SDS)-containing buffer with/without polyethylene glycol 20000 (PEG20000), urea-containing buffer, and FFPE-FASP protein preparation kit were compared for protein extraction from different types of rat FFPE tissues, including the heart, brain, liver, lung, and kidney. All of the samples were divided into two groups of laser microdissected (LMD) and non-LMD specimens. For both kinds of specimens, Zwittergent was the most efficient buffer for identifying peptides and proteins, was broadly applicable to different tissues without impairing the enzymatic digestion, and was well compatible with mass spectrometry analysis. As a high molecular weight carrier substance, PEG20000 improved the identification of peptides and proteins; however, such an advantage is limited to tissues containing submicrograms to micrograms of protein. Considering its low lytic strength, urea-containing buffer would not be the first alternative for protein recovery. In conclusion, Zwittergent 3–16 is an effective buffer for extracting proteins from FFPE specimens for downstream proteomics analysis. 相似文献