全文获取类型
收费全文 | 183篇 |
免费 | 14篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 5篇 |
2014年 | 4篇 |
2013年 | 8篇 |
2012年 | 11篇 |
2011年 | 6篇 |
2010年 | 8篇 |
2009年 | 2篇 |
2008年 | 4篇 |
2007年 | 1篇 |
2006年 | 7篇 |
2005年 | 3篇 |
2004年 | 6篇 |
2003年 | 5篇 |
2002年 | 7篇 |
2001年 | 4篇 |
2000年 | 6篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 6篇 |
1991年 | 4篇 |
1990年 | 12篇 |
1989年 | 9篇 |
1988年 | 2篇 |
1987年 | 7篇 |
1986年 | 2篇 |
1985年 | 6篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 8篇 |
1979年 | 5篇 |
1975年 | 6篇 |
1974年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1965年 | 1篇 |
1935年 | 1篇 |
排序方式: 共有197条查询结果,搜索用时 15 毫秒
1.
M. L. Miller A. Andringa J. Elliott K. Conwell Ii K. Dixon M. P. Carty 《Cell proliferation》1998,31(1):17-33
Numerous extra- and intracellular factors, including UV radiation, can initiate a programme of cell death by apoptosis. While apoptosis is commonly defined morphologically, the relationships between morphology and molecular events are not well established. To investigate these relationships in HeLa cells, eight morphometric criteria for cell proliferation and damage and 10 criteria for apoptotic phenotype were examined using light microscopy, and corroborated by ultrastructure and spectral imaging. They were identified (1) during a time course after irradiation with 0, 10 or 30 J/m2 UV-C; (2) after separation of apoptotic from normal cells on a Percoll gradient; and (3) after irradiation with UV-C plus perturbation of the apoptotic pathway by treatment with inhibitors of two caspases, ICE and CPP32. The number of cells in apoptosis increased in a dose-dependent manner after UV-C treatment. Centrifugation of irradiated cells on a Percoll gradient increased the collection of apoptotic cells tenfold. The stereotypical apoptotic phenotype, in which cells have deep cytoplasmic blebbing and highly condensed DNA, comprised only a few percent of all apoptoses, and was rarely seen in groups receiving caspase inhibitors. The most common apoptotic phenotype was a rounded cell with large spherical nucleolus and associated DNA. After treatment with UV-C plus inhibitors the apoptotic index was decreased by about 30% compared to UV-C radiation alone. These apoptotic cells had dark spherical cytoplasm with small blebs, greatly increased numbers of cytoplasmic ribosomes, abundant nucleolar material with a large separate granular component, and chromatin condensed at the nuclear membrane. Using the technique of spectral imaging, it was found that the spectrum obtained from the granular component of the nucleolus, which was elevated in apoptotic cells treated with UV-C plus inhibitors, was similar to the dense accumulation of ribosomes in the apoptotic cytoplasm. The data indicate that spectral imaging may be a useful tool for identifying and characterizing variations in the apoptotic process, and that the caspase inhibitors used here do not completely abolish UV-C induced apoptosis, but rather alter its incidence and progression. 相似文献
2.
Paul W. Brandt-Rauf Matthew R. Pincus Robert P. Carty Jack Lubowsky Matthew Avitable John Carucci Randall B. Murphy 《Journal of Protein Chemistry》1989,8(1):149-157
The binding of cancer cells to the basement membrane glycoprotein laminin appears to be a critical step in the metastatic process. This binding can be inhibited competitively by a specific pentapeptide sequence (Tyr-Ile-Gly-Ser-Arg) of the laminin B1 chain, and this peptide can prevent metastasis formationin vivo. However, other similar pentapeptide sequences (e.g., Tyr-Ile-Gly-Ser-Glu) have been found to be much less active in metastasis inhibition, raising the possibility that such amino acid substitutions produce structural changes responsible for altering binding to the laminin receptor. In this study, conformational energy analysis has been used to determine the three-dimensional structures of these peptides. The results indicate that the substitution of Glu for the terminal Arg produces a significant conformational change in the peptide backbone at the middle Gly residue. These results have important implications for the design of drugs that may be useful in preventing metastasis formation and tumor spread. 相似文献
3.
S D Kroll J Chen M De Vivo D J Carty A Buku R T Premont R Iyengar 《The Journal of biological chemistry》1992,267(32):23183-23188
4.
Nikisha Carty Nadège Berson Karsten Tillack Christina Thiede Diana Scholz Karsten Kottig Yalda Sedaghat Christina Gabrysiak George Yohrling Heinz von der Kammer Andreas Ebneth Volker Mack Ignacio Munoz-Sanjuan Seung Kwak 《PloS one》2015,10(4)
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin gene. Major pathological hallmarks of HD include inclusions of mutant huntingtin (mHTT) protein, loss of neurons predominantly in the caudate nucleus, and atrophy of multiple brain regions. However, the early sequence of histological events that manifest in region- and cell-specific manner has not been well characterized. Here we use a high-content histological approach to precisely monitor changes in HTT expression and characterize deposition dynamics of mHTT protein inclusion bodies in the recently characterized zQ175 knock-in mouse line. We carried out an automated multi-parameter quantitative analysis of individual cortical and striatal cells in tissue slices from mice aged 2–12 months and confirmed biochemical reports of an age-associated increase in mHTT inclusions in this model. We also found distinct regional and subregional dynamics for inclusion number, size and distribution with subcellular resolution. We used viral-mediated suppression of total HTT in the striatum of zQ175 mice as an example of a therapeutically-relevant but heterogeneously transducing strategy to demonstrate successful application of this platform to quantitatively assess target engagement and outcome on a cellular basis. 相似文献
5.
Nikisha Carty Kevin R. Nash Milene Brownlow Dana Cruite Donna Wilcock Maj-Linda B. Selenica Daniel C. Lee Marcia N. Gordon Dave Morgan 《PloS one》2013,8(3)
The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer’s disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry staining for total Aβ was significantly decreased in animals receiving the NEP-n and NEP-s but not for IDE-n or IDE-s in either the hippocampus or cortex. Congo red staining followed a similar trend revealing significant decreases in the hippocampus and the cortex for NEP-n and NEP-s treatment groups. Our results indicate that while rAAV-IDE does not have the same therapeutic potential as rAAV-NEP, rAAV-NEP-s and NEP-n are effective at reducing amyloid loads, and both of these vectors continue to have significant effects nine months post-injection. As such, they may be considered reasonable candidates for gene therapy trials in AD. 相似文献
6.
7.
Germline stem cells divide asymmetrically to produce one new daughter stem cell and one daughter cell that will subsequently undergo meiosis and differentiate to generate the mature gamete. The silent sister hypothesis proposes that in asymmetric divisions, the selective inheritance of sister chromatids carrying specific epigenetic marks between stem and daughter cells impacts cell fate. To facilitate this selective inheritance, the hypothesis specifically proposes that the centromeric region of each sister chromatid is distinct. In Drosophila germ line stem cells (GSCs), it has recently been shown that the centromeric histone CENP-A (called CID in flies)—the epigenetic determinant of centromere identity—is asymmetrically distributed between sister chromatids. In these cells, CID deposition occurs in G2 phase such that sister chromatids destined to end up in the stem cell harbour more CENP-A, assemble more kinetochore proteins and capture more spindle microtubules. These results suggest a potential mechanism of ‘mitotic drive’ that might bias chromosome segregation. Here we report that the inner kinetochore protein CENP-C, is required for the assembly of CID in G2 phase in GSCs. Moreover, CENP-C is required to maintain a normal asymmetric distribution of CID between stem and daughter cells. In addition, we find that CID is lost from centromeres in aged GSCs and that a reduction in CENP-C accelerates this loss. Finally, we show that CENP-C depletion in GSCs disrupts the balance of stem and daughter cells in the ovary, shifting GSCs toward a self-renewal tendency. Ultimately, we provide evidence that centromere assembly and maintenance via CENP-C is required to sustain asymmetric divisions in female Drosophila GSCs. 相似文献
8.
9.
Escherichia coli lipid A is a hexaacylated disaccharide of glucosamine with secondary laurate and myristate chains on the distal unit. Hexaacylated lipid A is a potent agonist of human Toll-like receptor 4, whereas its tetra- and pentaacylated precursors are antagonists. The inner membrane enzyme LpxL transfers laurate from lauroyl-acyl carrier protein to the 2'- R-3-hydroxymyristate moiety of the tetraacylated lipid A precursor Kdo 2-lipid IV A. LpxL has now been overexpressed, solubilized with n-dodecyl beta- d-maltopyranoside (DDM), and purified to homogeneity. LpxL migration on a gel filtration column is consistent with a molecular mass of 80 kDa, suggestive of an LpxL monomer (36 kDa) embedded in a DDM micelle. Mass spectrometry showed that deformylated LpxL was the predominant species, noncovalently bound to as many as 12 DDM molecules. Purified LpxL catalyzed not only the formation in vitro of Kdo 2-(lauroyl)-lipid IV A but also a slow second acylation, generating Kdo 2-(dilauroyl)-lipid IV A. Consistent with the Kdo dependence of crude LpxL in membranes, Kdo 2-lipid IV A is preferred 6000-fold over lipid IV A by the pure enzyme. Sequence comparisons suggest that LpxL shares distant homology with the glycerol-3-phosphate acyltransferase (GPAT) family, including a putative catalytic dyad located in a conserved H(X) 4D/E motif. Mutation of H132 or E137 to alanine reduces specific activity by over 3 orders of magnitude. Like many GPATs, LpxL can also utilize acyl-CoA as an alternative acyl donor, albeit at a slower rate. Our results show that the acyltransferases that generate the secondary acyl chains of lipid A are members of the GPAT family and set the stage for structural studies. 相似文献
10.
This paper comprises the scientific justification for the Farm Constructed Wetland (FCW) Design Manual for Northern Ireland and Scotland. Moreover, this document addresses an international audience interested in applying wetland systems in the wider agricultural context. Farm constructed wetlands combine farm wastewater (predominantly farmyard runoff) treatment with landscape and biodiversity enhancements, and are a specific application and class of integrated constructed wetlands (ICW), which have wider applications in the treatment of other wastewater types such as domestic sewage. The aim of this review paper is to propose guidelines highlighting the rationale for FCW, including key water quality management and regulatory issues, important physical and biochemical wetland treatment processes, assessment techniques for characterizing potential FCW sites and discharge options to water bodies. The paper discusses universal design, construction, planting, maintenance and operation issues relevant specifically for FCW in a temperate climate, but highlights also catchment-specific requirements to protect the environment. 相似文献