全文获取类型
收费全文 | 279篇 |
免费 | 26篇 |
出版年
2022年 | 5篇 |
2021年 | 6篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 2篇 |
2016年 | 4篇 |
2015年 | 13篇 |
2014年 | 17篇 |
2013年 | 16篇 |
2012年 | 30篇 |
2011年 | 20篇 |
2010年 | 15篇 |
2009年 | 18篇 |
2008年 | 22篇 |
2007年 | 16篇 |
2006年 | 12篇 |
2005年 | 11篇 |
2004年 | 20篇 |
2003年 | 9篇 |
2002年 | 11篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有305条查询结果,搜索用时 15 毫秒
81.
The ubiquitin ligase component Siah1a is required for completion of meiosis I in male mice 下载免费PDF全文
Dickins RA Frew IJ House CM O'Bryan MK Holloway AJ Haviv I Traficante N de Kretser DM Bowtell DD 《Molecular and cellular biology》2002,22(7):2294-2303
The mammalian Siah genes encode highly conserved proteins containing a RING domain. As components of E3 ubiquitin ligase complexes, Siah proteins facilitate the ubiquitination and degradation of diverse protein partners including beta-catenin, N-CoR, and DCC. We used gene targeting in mice to analyze the function of Siah1a during mammalian development and reveal novel roles in growth, viability, and fertility. Mutant animals have normal weights at term but are postnatally growth retarded, despite normal levels of pituitary growth hormone. Embryonic fibroblasts isolated from mutant animals grow normally. Most animals die before weaning, and few survive beyond 3 months. Serum gonadotropin levels are normal in Siah1a mutant mice; however, females are subfertile and males are sterile due to a block in spermatogenesis. Although spermatocytes in mutant mice display normal meiotic prophase and meiosis I spindle formation, they accumulate at metaphase to telophase of meiosis I and subsequently undergo apoptosis. The requirement of Siah1a for normal progression beyond metaphase I suggests that Siah1a may be part of a novel E3 complex acting late in the first meiotic division. 相似文献
82.
83.
Adenovirus Type 5 E4 Open Reading Frame 4 Protein Induces Apoptosis in Transformed Cells 总被引:6,自引:3,他引:3 下载免费PDF全文
Adenovirus type 5 E4 open reading frame 4 (E4orf4) protein has been previously shown to counteract transactivation of the junB and c-fos genes by cyclic AMP plus E1A protein and to interact with protein phosphatase 2A (PP2A). Here, we show that the wild-type E4orf4 protein induces apoptosis in the E1A-expressing 293 cells, in NIH 3T3 cells transformed with v-Ras, and in the lung carcinoma cell line H1299. The induction of apoptosis is not accompanied by enhanced levels of p53 in 293 cells and occurs in the absence of p53 in H1299 cells, indicating involvement of a p53-independent pathway. A mutant E4orf4 protein that had lost the ability to induce apoptosis also lost its ability to bind PP2A. We suggest that E4orf4 antagonizes continuous signals to proliferate, like those given by E1A or v-Ras, and that the conflicting signals lead to the induction of cell death. 相似文献
84.
Lens-Specific Gene Recruitment of ζ-Crystallin through Pax6, Nrl-Maf, and Brain Suppressor Sites 下载免费PDF全文
Ronit Sharon-Friling Jill Richardson Sally Sperbeck Douglas Lee Michael Rauchman Richard Maas Anand Swaroop Graeme Wistow 《Molecular and cellular biology》1998,18(4):2067-2076
ζ-Crystallin is a taxon-specific crystallin, an enzyme which has undergone direct gene recruitment as a structural component of the guinea pig lens through a Pax6-dependent mechanism. Tissue specificity arises through a combination of effects involving three sites in the lens promoter. The Pax6 site (ZPE) itself shows specificity for an isoform of Pax6 preferentially expressed in lens cells. High-level expression of the promoter requires a second site, identical to an αCE2 site or half Maf response element (MARE), adjacent to the Pax6 site. A promoter fragment containing Pax6 and MARE sites gives lens-preferred induction of a heterologous promoter. Complexes binding the MARE in lens nuclear extracts are antigenically related to Nrl, and cotransfection with Nrl elevates ζ-crystallin promoter activity in lens cells. A truncated ζ promoter containing Nrl-MARE and Pax6 sites has a high level of expression in lens cells in transgenic mice but is also active in the brain. Suppression of the promoter in the brain requires sequences between −498 and −385, and a site in this region forms specific complexes in brain extract. A three-level model for lens-specific Pax6-dependent expression and gene recruitment is suggested: (i) binding of a specific isoform of Pax6; (ii) augmentation of expression through binding of Nrl or a related factor; and (iii) suppression of promoter activity in the central nervous system by an upstream negative element in the brain but not in the lens. 相似文献
85.
Ronit Pinkas-Kramarski Maya Shelly Bradley C. Guarino Ling Mei Wang Ljuba Lyass Iris Alroy Maurizio Alimandi Angera Kuo James D. Moyer Sara Lavi Miriam Eisenstein Barry J. Ratzkin Rony Seger Sarah S. Bacus Jacalyn H. Pierce Glenn C. Andrews Yosef Yarden 《Molecular and cellular biology》1998,18(12):7602
86.
Ronit Har-el Esther Marva Mordechai Chevion Jacob Golenser 《Free radical research》1993,18(5):279-290
Based on the unusually high and stage-dependant susceptibility of Plasmodia to oxidant stress it has been proposed that during parasite development, increasing levels of redox-active forms of iron are gradually released. The purpose of this study was to examine this proposal by using an assay monitoring the levels of available forms of iron for redox reactions. Ascorbate-driven and iron-mediated degradation of adventitious DNA served as the basis for this functional assay.
Incubation of DNA with lysate from infected RBC caused massive degradation, which was dose, time-and parasite-stage dependent. In contrast, lysate from non-infected RBC did not induce DNA degradation. Likewise, lysate only from infected RBC enhanced the aerobic oxidation of ascorbate. These effects on both reactions, DNA degradation and ascorbate oxidation, could be reconstructed with hemin, instead of lysate. Also, chelators exerted similar effects on both reactions.
The results suggest that increased levels of redox-active forms of iron are liberated during parasite development. We propose that hemin or hemin-like structures are the appropriate candidates which could catalyze oxidative stress and deregulate the delicate redox balance of the host-parasite system. 相似文献
Incubation of DNA with lysate from infected RBC caused massive degradation, which was dose, time-and parasite-stage dependent. In contrast, lysate from non-infected RBC did not induce DNA degradation. Likewise, lysate only from infected RBC enhanced the aerobic oxidation of ascorbate. These effects on both reactions, DNA degradation and ascorbate oxidation, could be reconstructed with hemin, instead of lysate. Also, chelators exerted similar effects on both reactions.
The results suggest that increased levels of redox-active forms of iron are liberated during parasite development. We propose that hemin or hemin-like structures are the appropriate candidates which could catalyze oxidative stress and deregulate the delicate redox balance of the host-parasite system. 相似文献
87.
Low stimulated IL-4 secretion in PBMC from patients with chronic idiopathic urticaria 总被引:9,自引:0,他引:9
Confino-Cohen R Goldberg A Aharoni D Naiman L Buchs A Weiss M Weissgarten J Rapoport MJ 《Cytokine》2004,27(2-3):74-80
An imbalance between the Th1 and Th2 arms of the cellular immune system has been reported in several autoimmune diseases but not in chronic idiopathic urticaria (CIU). Peak, total secretion and secretory pattern of the Th1 cytokines (IFNgamma and IL-2) and Th2 cytokines (IL-4 and IL-10) were determined in resting and stimulated peripheral blood mononuclear cells (PBMC) from nineteen CIU patients, six acute urticaria patients and twelve controls. Stimulated IL-4 secretion was significantly reduced in CIU patients as indicated by their five- and three-fold lower peak levels and total IL-4 secretion, respectively. The IL-4 secretory pattern overtime was also markedly different in patients and controls. The late secretion of IFNgamma at 144 h was also reduced in CIU patients. These aberrations were not detectable in AU patients. Secretion of IL-2 was lower in CIU and AU patients as compared to controls while IL-10 secretion was comparable in the three groups. Our data demonstrate for the first time a predominantly reduced IL-4 secretion in CIU patients. This is associated with reduced secretion of both IL-2 and IFNgamma. These findings indicate a generalized down-regulation of both Th1 and Th2 cytokines' secretion in CIU. 相似文献
88.
Inhibition of angiogenesis by THAM-derived cotelomers endowed with thalidomide moieties 总被引:2,自引:0,他引:2
Périno S Contino-Pépin C Satchi-Fainaro R Butterfield C Pucci B 《Bioorganic & medicinal chemistry letters》2004,14(2):421-425
The synthesis of a tris(hydroxymethyl)acrylamidomethane (THAM)-derived cotelomer endowed with thalidomide units and a preliminary assessment of its biological activity are described. 4-Carboxy thalidomide and 4-(N-acryloyl) lysine thalidomide derivatives were prepared. The polymerization of these compounds with THAM in the presence of octanethiol as transfer reagent provided a water-soluble telomer bearing several thalidomide units. The ability of this telomer to inhibit angiogenesis in a mouse model of corneal neovascularization was compared to 4-carboxy thalidomide and thalidomide. A significant inhibition in area of neovascularization stimulated by a bFGF pellet was observed only in the mice treated with the telomer. 相似文献
89.
Natia Japaridze Muthuraman Muthuraman Christine Reinicke Friederike Moeller Abdul Rauf Anwar Kidist Gebremariam Mideksa Ronit Pressler Günther Deuschl Ulrich Stephani Michael Siniatchkin 《PloS one》2015,10(4)
Introduction
Burst-suppression (BS) is an electroencephalography (EEG) pattern consisting of alternant periods of slow waves of high amplitude (burst) and periods of so called flat EEG (suppression). It is generally associated with coma of various etiologies (hypoxia, drug-related intoxication, hypothermia, and childhood encephalopathies, but also anesthesia). Animal studies suggest that both the cortex and the thalamus are involved in the generation of BS. However, very little is known about mechanisms of BS in humans. The aim of this study was to identify the neuronal network underlying both burst and suppression phases using source reconstruction and analysis of functional and effective connectivity in EEG.Material/Methods
Dynamic imaging of coherent sources (DICS) was applied to EEG segments of 13 neonates and infants with burst and suppression EEG pattern. The brain area with the strongest power in the analyzed frequency (1–4 Hz) range was defined as the reference region. DICS was used to compute the coherence between this reference region and the entire brain. The renormalized partial directed coherence (RPDC) was used to describe the informational flow between the identified sources.Results/Conclusion
Delta activity during the burst phases was associated with coherent sources in the thalamus and brainstem as well as bilateral sources in cortical regions mainly frontal and parietal, whereas suppression phases were associated with coherent sources only in cortical regions. Results of the RPDC analyses showed an upwards informational flow from the brainstem towards the thalamus and from the thalamus to cortical regions, which was absent during the suppression phases. These findings may support the theory that a “cortical deafferentiation” between the cortex and sub-cortical structures exists especially in suppression phases compared to burst phases in burst suppression EEGs. Such a deafferentiation may play a role in the poor neurological outcome of children with these encephalopathies. 相似文献90.
Carmen Mikacenic William O. Hahn Brenda L. Price Susanna Harju-Baker Ronit Katz Kevin C. Kain Jonathan Himmelfarb W. Conrad Liles Mark M. Wurfel 《PloS one》2015,10(10)