全文获取类型
收费全文 | 3328篇 |
免费 | 31篇 |
国内免费 | 45篇 |
出版年
2023年 | 16篇 |
2022年 | 13篇 |
2021年 | 22篇 |
2020年 | 40篇 |
2019年 | 68篇 |
2018年 | 92篇 |
2017年 | 26篇 |
2016年 | 32篇 |
2015年 | 92篇 |
2014年 | 199篇 |
2013年 | 174篇 |
2012年 | 151篇 |
2011年 | 228篇 |
2010年 | 212篇 |
2009年 | 205篇 |
2008年 | 227篇 |
2007年 | 235篇 |
2006年 | 152篇 |
2005年 | 126篇 |
2004年 | 159篇 |
2003年 | 103篇 |
2002年 | 88篇 |
2001年 | 40篇 |
2000年 | 55篇 |
1999年 | 45篇 |
1998年 | 44篇 |
1997年 | 40篇 |
1996年 | 40篇 |
1995年 | 45篇 |
1994年 | 30篇 |
1993年 | 35篇 |
1992年 | 34篇 |
1991年 | 27篇 |
1990年 | 22篇 |
1989年 | 14篇 |
1988年 | 20篇 |
1987年 | 30篇 |
1986年 | 13篇 |
1985年 | 18篇 |
1984年 | 24篇 |
1983年 | 19篇 |
1982年 | 30篇 |
1981年 | 17篇 |
1980年 | 27篇 |
1979年 | 22篇 |
1978年 | 7篇 |
1977年 | 12篇 |
1976年 | 11篇 |
1974年 | 5篇 |
1972年 | 5篇 |
排序方式: 共有3404条查询结果,搜索用时 15 毫秒
51.
Janka Kubálková Vladimíra Tomečková Pál Perjési Juraj Guzy 《Central European Journal of Biology》2009,4(1):90-96
The cytotoxic and protective effects of selected synthetic chalcone analogues have been shown in previous studies. We studied
their cytotoxic effect on the modification of mitochondrial membrane potential and on DNA. The first spectral information
about the methoxy group as well as the dimethylamino substituent in E-2-arylmethylene-1-benzosuberones molecule was obtained
by absorption and emission spectra. The cytotoxic effect of both cyclic chalcone analogues on DNA were detected by alkaline
single-cell gel electrophoresis. Better fluorescent chalcone analogue E-2-(4′-dimethylamino-benzylidene)-1-benzosuberone was
studied further in fresh isolated mitochondria. The decrease of rat liver mitochondria membrane potential (Δψ) was observed
by fluorescence emission spectra. For the collapsing of mitochondrial potentials and as the negative control of mitochondrial
function the CCCP uncoupler was used. The absorption maximum of the methoxy group was found at a shorter wavelength (λ = 335
nm) than that of the dimethylamino group (λ = 406 nm). The excitation spectra were very similar to the absorption spectra
for both molecules but the emission spectra showed a better fluorescence for dimethylamino derivative. After the addition
of E-2-(4′-dimethylamino-benzylidene)-1-benzosuberone to the intact mitochondria the decrease of mitochondrial membrane potential
Δψ was observed by emisssion fluorescence spectra. Both cyclic chalcone analogues induced DNA damage, which was detected by
alkaline comet assay. Mainly the apoptotic cells were detected, but necrotic cells were also present. Similarities in the
percentages of DNA migration from the head were observed in both treatment groups. Both benzosuberones, with dimethylamino-
and methoxy- substituent, were very active biologically, as shown by DNA results of the comet assay. Due to its better fluorescence
properties, only the fluorophore with dimethylamino substituent was selected for further study of the function of rat liver
mitochondria. Decline of mitochondrial function as well as mitochondrial DNA damage were evident between experimental and
control groups. 相似文献
52.
Natalie Lefort Zhengping Yi Benjamin Bowen Brian Glancy Eleanna A. De Filippis Rebekka Mapes Hyonson Hwang Charles R. Flynn Wayne T. Willis Anthony Civitarese Kurt Hjlund Lawrence J. Mandarino 《Journal of Proteomics》2009,72(6):1046
Mitochondria can be isolated from skeletal muscle in a manner that preserves tightly coupled bioenergetic function in vitro. The purpose of this study was to characterize the composition of such preparations using a proteomics approach. Mitochondria isolated from human vastus lateralis biopsies were functional as evidenced by their response to carbohydrate and fat-derived fuels. Using one-dimensional gel electrophoresis and HPLC-ESI-MS/MS, 823 unique proteins were detected, and 487 of these were assigned to the mitochondrion, including the newly characterized SIRT5, MitoNEET and RDH13. Proteins detected included 9 of the 13 mitochondrial DNA-encoded proteins and 86 of 104 electron transport chain (ETC) and ETC-related proteins. In addition, 59 of 78 proteins of the 55S mitoribosome, several TIM and TOM proteins and cell death proteins were present. This study presents an efficient method for future qualitative assessments of proteins from functional isolated mitochondria from small samples of healthy and diseased skeletal muscle. 相似文献
53.
用光镜和电镜观察羽叶薰衣草(Lavandula pinnata L.)雄性不育小孢子发育过程的细胞形态学特征.结果表明:羽叶薰衣草花药4枚,每枚花药通常具4个小孢子囊.花药壁发育为双子叶型,从外向内分为表皮、药室内壁、中层和绒毡层4层细胞.减数分裂形成的四分体为四面体及十字交叉型.小孢子的发育过程可分为造孢细胞期、减数分裂时期、小孢子发育早期、小孢子发育晚期.未观察到二胞花粉期和成熟花粉期.羽叶薰衣草花粉败育主要发生在单核花粉时期,细胞内物质解体并逐渐消失变成空壳花粉或花粉皱缩变形成为各种畸形的败育花粉.在此之前小孢子的发育正常.羽叶薰衣草小孢子不育机制体现在绒毡层过早解体、四分体时期以后各细胞中线粒体结构不正常、胼胝质壁与小孢子母细胞脱离、花药壁细胞中淀粉出现时间异常等. 壁发育为双子叶型,从外向内分为表皮、药室内壁、中层和绒毡层4层细胞.减数分裂形成的四分体为四面体及十字交叉型.小孢子的发育过程可分为造孢细胞期、减数分裂时期、小孢子发育早期、小孢子发育晚期.未观察到二胞花粉期和成熟花粉期.羽叶薰衣草花粉败育主要发生在单核花粉时期,细胞内物质解体并逐渐消失变成空壳花粉或花粉皱缩变形成为各种畸形的败育花粉.在此 前小孢子的发育正常.羽叶薰衣草小孢子不育机制体现在绒毡层过早解体、四分体时期以后各细胞中线粒体结构不正常、胼胝质壁与小孢子母细胞脱离、花药壁细胞中淀粉出现时间异常等. 壁发育为双子叶型,从外向内分为表皮、药室内壁、中层和绒毡层4层细胞.减数分裂形成的四分体为四 相似文献
54.
Mordhwaj S. Parihar Arti Parihar Masayo Fujita Makoto Hashimoto Pedram Ghafourifar 《The international journal of biochemistry & cell biology》2009,41(10):2015-2024
Overexpression of alpha-synuclein and oxidative stress has been implicated in the neuronal cell death in Parkinson's disease. Alpha-synuclein associates with mitochondria and excessive accumulation of alpha-synuclein causes impairment of mitochondrial functions. However, the mechanism of mitochondrial impairment caused by alpha-synuclein is not fully understood. We recently reported that alpha-synuclein associates with mitochondria and that overexpression of alpha-synuclein causes nitration of mitochondrial proteins and release of cytochrome c from the mitochondria [Parihar M.S., Parihar A., Fujita M., Hashimoto M., Ghafourifar P. Mitochondrial association of alpha-synuclein causes oxidative stress. Cell Mol Life Sci. 2008a;65:1272–1284]. The present study shows that overexpression of alpha-synuclein A53T or A30P mutants or wild-type in human neuroblastoma cells augmented aggregation of alpha-synuclein. Immunoblotting and immuno-gold electron transmission microscopy show localization of alpha-synuclein aggregates within the mitochondria of overexpressing cells. Overexpressing cells show increased mitochondrial reactive oxygen species, increased protein tyrosine nitration, decreased mitochondrial transmembrane potential, and hampered cellular respiration. These findings suggest an important role for mitochondria in cellular responses to alpha-synuclein. 相似文献
55.
Structural and functional link between the mitochondrial network and the endoplasmic reticulum 总被引:1,自引:0,他引:1
Carlotta Giorgi Diego De Stefani Angela Bononi Rosario Rizzuto Paolo Pinton 《The international journal of biochemistry & cell biology》2009,41(10):1817-1827
Mitochondrial and endoplasmic reticulum (ER) networks are fundamental for the maintenance of cellular homeostasis and for determination of cell fate under stress conditions. Recent structural and functional studies revealed the interaction of these networks. These zones of close contact between ER and mitochondria called MAM (mitochondria associated membranes) support communication between the two organelles including bioenergetics and cell survival. The existence of macromolecular complexes in these contact sites has also been revealed. In this contribution, we will review: (i) the ER and mitochondria structure and their dynamics, (ii) the basic principles of ER mitochondrial Ca2+ transport, (iii) the physiological/pathological role of this cross-talk. 相似文献
56.
Valeriy Lukyanenko Aristide Chikando W.J. Lederer 《The international journal of biochemistry & cell biology》2009,41(10):1957-1971
Ca2+ signaling is of vital importance to cardiac cell function and plays an important role in heart failure. It is based on sarcolemmal, sarcoplasmic reticulum and mitochondrial Ca2+ cycling. While the first two are well characterized, the latter remains unclear, controversial and technically challenging.In mammalian cardiac myocytes, Ca2+ influx through L-type calcium channels in the sarcolemmal membrane triggers Ca2+ release from the nearby junctional sarcoplasmic reticulum to produce Ca2+ sparks. When this triggering is synchronized by the cardiac action potential, a global [Ca2+]i transient arises from coordinated Ca2+ release events. The ends of intermyofibrillar mitochondria are located within 20 nm of the junctional sarcoplasmic reticulum and thereby experience a high local [Ca2+] during the Ca2+ release process. Both local and global Ca2+ signals may thus influence calcium signaling in mitochondria and, reciprocally, mitochondria may contribute to the local control of calcium signaling. In addition to the intermyofibrillar mitochondria, morphologically distinct mitochondria are also located in the perinuclear and subsarcolemmal regions of the cardiomyocyte and thus experience a different local [Ca2+].Here we review the literature in regard to several issues of broad interest: (1) the ultrastructural basis for mitochondrion – sarcoplasmic reticulum cross-signaling; (2) mechanisms of sarcoplasmic reticulum signaling; (3) mitochondrial calcium signaling; and (4) the possible interplay of calcium signaling between the sarcoplasmic reticulum and adjacent mitochondria.Finally, this review discusses experimental findings and mathematical models of cardiac calcium signaling between the sarcoplasmic reticulum and mitochondria, identifies weaknesses in these models, and suggests strategies and approaches for future investigations. 相似文献
57.
Jean Velours Alain Dautant Bndicte Salin Isabelle Sagot Daniel Brthes 《The international journal of biochemistry & cell biology》2009,41(10):1783-1789
The mitochondrial F1F0-ATP synthase adopts supramolecular structures. The interaction domains between monomers involve components belonging to the F0 domains. In Saccharomyces cerevisiae, alteration of these components destabilizes the oligomeric structures, leading concomitantly to the appearance of monomeric species of ATP synthase and anomalous mitochondrial morphologies in the form of onion-like structures. The mitochondrial ultrastructure at the cristae level is thus modified. Electron microscopy on cross-sections of wild type mitochondria display many short cristae with narrowed intra-cristae space, whereas yeast mutants defected in supramolecular ATP synthases assembly present a low number of large lamellar cristae of constant thickness and traversing the whole organelle. The growth of these internal structures leads finally to mitochondria with sphere-like structures with a mean diameter of 1 μm that are easily identified by epifluorescence microscopy. As a result, ATP synthase is an actor of the mitochondrial ultrastructure in yeast. This paper reviews the ATP synthase components whose modifications lead to anomalous mitochondrial morphology and also provides a schema showing the formation of the so-called onion-like structures. 相似文献
58.
59.
Role of apoptosis in cardiovascular disease 总被引:2,自引:0,他引:2
Youngil Lee Åsa B. Gustafsson 《Apoptosis : an international journal on programmed cell death》2009,14(4):536-548
Apoptosis plays a key role in the pathogenesis in a variety of cardiovascular diseases due to loss of terminally differentiated
cardiac myocytes. Cardiac myocytes undergoing apoptosis have been identified in tissue samples from patients suffering from
myocardial infarction, diabetic cardiomyopathy, and end-stage congestive heart failure. Apoptosis is a highly regulated program
of cell death and can be mediated by death receptors in the plasma membrane, as well as the mitochondria and the endoplasmic
reticulum. The cell death program is activated in cardiac myocytes by various stressors including cytokines, increased oxidative
stress and DNA damage. Many studies have demonstrated that inhibition of apoptosis is cardioprotective and can prevent the
development of heart failure. This review provides a current overview of the evidence of apoptosis in cardiovascular diseases
and discusses the molecular pathways involved in cardiac myocyte apoptosis. 相似文献