全文获取类型
收费全文 | 136篇 |
免费 | 26篇 |
专业分类
162篇 |
出版年
2016年 | 1篇 |
2015年 | 2篇 |
2014年 | 3篇 |
2013年 | 2篇 |
2012年 | 2篇 |
2011年 | 9篇 |
2010年 | 2篇 |
2009年 | 5篇 |
2007年 | 6篇 |
2006年 | 3篇 |
2005年 | 4篇 |
2004年 | 3篇 |
2003年 | 7篇 |
2002年 | 2篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 8篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 1篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1976年 | 1篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1969年 | 5篇 |
1968年 | 2篇 |
1966年 | 1篇 |
1965年 | 2篇 |
1955年 | 1篇 |
1938年 | 1篇 |
排序方式: 共有162条查询结果,搜索用时 15 毫秒
1.
Nonrandom induction of pyrimidine-pyrimidone (6-4) photoproducts in ultraviolet-irradiated human chromatin 总被引:8,自引:0,他引:8
Radioimmunoassays that detect pyrimidine-pyrimidone (6-4) photoproducts and cyclobutane dimers were used to determine the relative induction of these photoproducts in nucleosomal (core) and internucleosomal (linker) DNA in human cell chromatin irradiated with UV light. Cyclobutane dimers were formed in equal amounts/nucleotide in core and linker DNA, whereas (6-4) photoproducts occurred with 6-fold greater frequency/nucleotide in linker DNA. 相似文献
2.
3.
4.
Xeroderma pigmentosum variant (XP-V) cells lack the damage-specific DNA polymerase eta and have normal excision repair but show defective DNA replication after UV irradiation. Previous studies using cells transformed with SV40 or HPV16 (E6/E7) suggested that the S-phase response to UV damage is altered in XP-V cells with non-functional p53. To investigate the role of p53 directly we targeted p53 in normal and XP-V fibroblasts using short hairpin RNA. The shRNA reduced expression of p53, and the downstream cell cycle effector p21, in control and UV irradiated cells. Cells accumulated in late S phase after UV, but after down-regulation of p53 they accumulated earlier in S. Cells in which p53 was inhibited showed ongoing genomic instability at the replication fork. Cells exhibited high levels of UV induced S-phase gammaH2Ax phosphorylation representative of exposed single strand regions of DNA and foci of Mre11/Rad50/Nbs1 representative of double strand breaks. Cells also showed increased variability of genomic copy numbers after long-term inhibition of p53. Inhibition of p53 expression dominated the DNA damage response. Comparison with earlier results indicates that in virally transformed cells cellular targets other than p53 play important roles in the UV DNA damage response. 相似文献
5.
Andrey V. Kajava Naiqian Cheng Ryan Cleaver Martin Kessel Martha N. Simon Eve Willery Francoise Jacob-Dubuisson Camille Locht Alasdair C. Steven 《Molecular microbiology》2001,42(2):279-292
Bordetella pertussis establishes infection by attaching to epithelial cells of the respiratory tract. One of its adhesins is filamentous haemagglutinin (FHA), a 500-A-long secreted protein that is rich in beta-structure and contains two regions, R1 and R2, of tandem 19-residue repeats. Two models have been proposed in which the central shaft is (i) a hairpin made up of a pairing of two long antiparallel beta-sheets; or (ii) a beta-helix in which the polypeptide chain is coiled to form three long parallel beta-sheets. We have analysed a truncated variant of FHA by electron microscopy (negative staining, shadowing and scanning transmission electron microscopy of unstained specimens): these observations support the latter model. Further support comes from detailed sequence analysis and molecular modelling studies. We applied a profile search method to the sequences adjacent to and between R1 and R2 and found additional "covert" copies of the same motifs that may be recognized in overt form in the R1 and R2 sequence repeats. Their total number is sufficient to support the tenet of the beta-helix model that the shaft domain--a 350 A rod--should consist of a continuous run of these motifs, apart from loop inserts. The N-terminus, which does not contain such repeats, was found to be weakly homologous to cyclodextrin transferase, a protein of known immunoglobulin-like structure. Drawing on crystal structures of known beta-helical proteins, we developed structural models of the coil motifs putatively formed by the R1 and R2 repeats. Finally, we applied the same profile search method to the sequence database and found several other proteins--all large secreted proteins of bacterial provenance--that have similar repeats and probably also similar structures. 相似文献
6.
Xeroderma pigmentosum variant (XPV) cells lack the damage-specific polymerase eta and undergo a protracted arrest at the S phase checkpoint(s) following UV damage. The S phase checkpoints encompass several qualitatively different processes, and stimulate downstream events that are dependent on the functional state of p53. Primary fibroblasts with wild-type p53 arrest in S, and require a functional polymerase eta (pol eta) to carry out bypass replication, but do not recruit recombination factors for recovery. XPV cells with non-functional p53, as a result of transformation by SV40 or HPV16 (E6/E7), recruit the hMre11/hRad50/Nbs1 complex to arrested replication forks, coincident with PCNA, whereas normal transformed cells preferentially use the pol eta bypass replication pathway. The formation of hMre11 foci implies that arrested replication forks rapidly undergo a collapse involving double strand breakage and rejoining. Apoptosis occurs after UV only in cells transformed by SV40, and not in normal or XPV fibroblasts or HPV16 (E6/E7) transformed cells. Conversely, ultimate cell survival in XPV cells was much less in HPV16 (E6/E7) transformed cells than in SV40 transformed cells, indicating that apoptosis was not a reliable predictor of cell survival. Inhibition of p53 transactivation by pifithrin-alpha or inhibition of protein synthesis by cycloheximide did not induce hMre11 foci or apoptosis in UV damaged fibroblasts. Inhibition of kinase activity with wortmannin did not increase killing by UV, unlike the large increase seen with caffeine. Since HPV16 (E6/E7) transformed XPV cells were highly UV sensitive and not further sensitized by caffeine, it appears likely that caffeine sensitization proceeds through a p53 pathway. The S phase checkpoints are therefore, a complex set of different checkpoints that are coordinated by p53 with the capacity to differentially modulate cell survival, apoptosis, bypass replication and hMre11 recombination. 相似文献
7.
Photoreactivation 总被引:2,自引:0,他引:2
Cleaver JE 《DNA Repair》2003,2(5):629, 637-629, 638
Kelner and Dulbecco first reported in the 1940s and 1950s the reversal of ultraviolet damage in bacteria and phage by illumination with visible light. The first publications, reprinted here, represented the discovery of a widespread repair mechanism that was named "photoreactivation" (PHR), that directly reversed photoproducts to their individual pyrimidine components. Between them, these pioneers demonstrated that photoreactivation had a cellular basis, could be defined by wavelength optima indicating specific molecular photoreceptors, and had a widespread phyletic distribution except for its absence from placental mammals. 相似文献
8.
Endothelial signaling during development 总被引:15,自引:0,他引:15
Blood vessels perfuse all tissues in the body and mediate vital metabolic exchange between tissues and blood. Increasing evidence, however, points to a direct role for paracrine signaling between blood vessel cells and surrounding target organ cells, during embryonic development and cell differentiation. Understanding the nature of this signaling and its heterogeneity, both in the embryo and in adult tissues, may not only provide insights into mechanisms for normal developmental cell fate decisions, but could also lead to novel targeted therapeutic approaches for a variety of diseases such as heart disease, diabetes or cancer. 相似文献
9.
Patterson KD Cleaver O Gerber WV White FG Krieg PA 《Development genes and evolution》2000,210(3):140-144
The BarH1 and BarH2 homeobox genes are coexpressed in cells of the fly retina and in the central and peripheral nervous systems. The fly Bar genes are required for normal development of the eye and external sensory organs. In Xenopus we have identified two distinct vertebrate Bar-related homeobox genes, XBH1 and XBH2. XBH1 is highly related in sequence and expression pattern to a mammalian gene, MBH1, suggesting that they are orthologues. XBH2 has not previously been identified but is clearly related to the Drosophila
Bar genes. During early Xenopus embryogenesis XBH1 and XBH2 are expressed in overlapping regions of the central nervous system. XBH1, but not XBH2, is expressed in the developing retina. By comparing the expression of XBH1 with that of hermes, a marker of differentiated retinal ganglion cells, we show that XBH1 is expressed in retinal ganglion cells during the differentiation process, but is down-regulated as cells become terminally
differentiated.
Received: 12 August 1999 / Accepted: 5 October 1999 相似文献
10.
On the basis of qualitative assays, quiescent lymphocytes have previously been reported to have numerous DNA strand breaks, which are thought to be repaired after mitogenic stimulation by a process associated with poly(ADP-ribosyl)ation. Using alkaline elution, a very sensitive assay for quantifying DNA single-strand breakage, we found no evidence for a high frequency of DNA strand breaks in unstimulated human peripheral blood lymphocytes. No differences in elution profiles were observed between unstimulated lymphocytes and lymphocytes 4 or 48 h after addition of the mitogen phytohemagglutinin (PHA). Furthermore, addition of 3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) synthetase, or aphidicolin, an inhibitor of DNA polymerase alpha, did not increase the amount of DNA eluting from the filter after PHA stimulation. In contrast to reported studies of mouse splenic lymphocytes, we found that human lymphocytes were able to replicate and divide in the presence of the ADP-ribosylation inhibitor. Human lymphocytes were also capable of proliferating in nicotinamide-free medium, with or without 3AB, indicating that ADP-ribosylation is not a requirement for lymphocyte differentiation. We therefore consider it unlikely that peripheral human lymphocytes contain significant numbers of strand breaks that play any role in their stimulation or differentiation in response to PHA. 相似文献