全文获取类型
收费全文 | 357篇 |
免费 | 117篇 |
出版年
2022年 | 5篇 |
2021年 | 8篇 |
2020年 | 3篇 |
2019年 | 10篇 |
2018年 | 17篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 20篇 |
2014年 | 12篇 |
2013年 | 22篇 |
2012年 | 25篇 |
2011年 | 25篇 |
2010年 | 16篇 |
2009年 | 18篇 |
2008年 | 22篇 |
2007年 | 21篇 |
2006年 | 15篇 |
2005年 | 14篇 |
2004年 | 23篇 |
2003年 | 16篇 |
2002年 | 14篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 12篇 |
1998年 | 4篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1992年 | 9篇 |
1991年 | 4篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 10篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1972年 | 1篇 |
排序方式: 共有474条查询结果,搜索用时 15 毫秒
11.
A 31-amino-acid N-terminal extension regulates c-Crk binding to tyrosine-phosphorylated proteins. 总被引:4,自引:2,他引:2
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Overproduction of v-Crk, but not of c-Crk, in chicken embryo fibroblasts results in cell transformation. The transforming activity of v-Crk mutants correlates with their ability to cause increased tyrosine phosphorylation of specific cellular proteins, a property that depends on the binding of v-Crk to phosphotyrosine residues via its SH2 domain. In this study, proteins translated in rabbit reticulocyte lysates were used to analyze interactions between Crk derivatives and tyrosine-phosphorylated proteins, particularly the epidermal growth factor (EGF) receptor. The results demonstrate that the binding affinity of c-Crk is much lower than that of v-Crk, despite the fact that both proteins contain identical SH2 domains. Moreover, a 31-amino-acid N-terminal extension of c-Crk, resulting from upstream translational initiation at a CUG codon, significantly increases the ability of the resulting protein to bind to phosphotyrosine-containing proteins. Of those 31 amino acids, 24 can be found in the 27-amino-acid region between Gag and Crk sequences in v-Crk, and removal of this region results in a protein with lower affinity toward the EGF receptor. In addition, fusion of Gag to the amino terminus of c-Crk yields a protein with a binding activity that is lower than that of v-Crk but significantly higher than that of c-Crk without the fusion. These data suggest that sequences N terminal to the Crk SH2 regulate binding activity to tyrosine-phosphorylated proteins and that the amino acids encoded immediately 5' to the c-Crk initiator AUG specifically increase binding affinity. In contrast, deletion of one or two SH3 domains of c-Crk proteins did not change their affinity for the EGF receptor. These results were confirmed in vivo by using A431-derived cell lines overproducing either the chicken c-Crk protein or c-Crk with the 31-amino-acid N-terminal extension. Furthermore, the in vivo experiments suggest that binding of Crk proteins to the stimulated EGF receptor results in Crk phosphorylation and subsequent loss of binding affinity. 相似文献
12.
We have suggested previously that the amino-terminal 8 kilodaltons of pp60src may serve as a structural hydrophobic domain through which pp60src attaches to plasma membranes. Two isolates of recovered avian sarcoma viruses (rASVs), 1702 and 157, encode pp60src proteins that have alterations in this amino-terminal region. The rASV 1702 src protein (56 kilodaltons) and the 157 src protein (62.5 kilodaltons) show altered membrane association, and fractionate largely as soluble, cytoplasmic proteins in aqueous buffers, in contrast with the membrane association of more than 80% of the src protein of standard avian sarcoma virus under the identical fractionation procedure. Plasma membranes purified from cells transformed by these rASVs contain less than 10% of the amount of pp60src found in membranes purified from cells transformed by Rous sarcoma virus or control rASVs. The altered membrane association of these src proteins had little or no effect on the properties of chick embryo fibroblasts transformed in monolayer culture. In contrast, rASV 1702 showed reduced in vivo tumorigenicity compared with Rous sarcoma virus or with other rASVs that encode membrane-associated src proteins. Rous sarcoma virus-induced tumors are malignant, poorly differentiated sarcomas that are lethal to their hosts. rASV 1702 induces a benign, differentiated sarcoma that regresses and is not lethal to its hosts. These data support the role of amino-terminal sequences in the membrane association of pp60src, and suggest that the amino terminus of pp60src may have a critical role in the promotion of in vivo tumorigenicity. 相似文献
13.
H Fushimi S Tsukuda T Hanafusa Y Matsuyuki M Nishikawa S Ishihara K Kanao 《Endocrinologia japonica》1980,27(6):679-687
Twenty five cases of insulin autoimmune syndrome including this case has been reported so far without having the pathogenesis clarified. This paper describes a case which suggests one aspect of pathogenesis. The patient, a housewife concurrently had insulinoma and severe rheumatoid arthritis, complaining of hypoglycemic syncope attacks. During the attacks her blood sugar levels ranged from 19 to 22 mg%. Her serum extractable immunoreactive insulin (IRI) and insulin binding antibody levels were 557 microunits/ml and 0.390 mU/ml, respectively. gamma-Globulin-bound insulin was also measured electrophoretically. Bio-Gel P 10 column chromatography eluted almost all IRI at the void volume at pH 7.4 and a smaller but significant IRI peak also at pH 3.0. Selective angiography revealed a tumor-like staining in the pancreas body. Pancreatectomy relieved her of hypoglycemic attacks. Histology disclosed two small insulinomas. Insulinoma, rheumatoid arthritis and insulin autoimmune syndrome coexisted in this case, suggesting some causal relationship among them. 相似文献
14.
Characterization of some isolates of newly recovered avian sarcoma virus. 总被引:13,自引:8,他引:5
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We previously reported the isolation of a newly recovered avian sarcoma virus (rASV) from tumors of chickens injected with transformation-defective (td) mutants of the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV). In this paper, we present further biological and biochemical characterization of the recovered sarcoma viruses. High titers of rASV's were generally obtained by cocultivation of tumor cells with normal chicken embryo fibroblasts or by homogenization of tumor tissues. Most rASV isolates were similar to SR-RSV, subgroup A (SR-RSV-A), in their growth characteristics and were nondefective in replication. The subgroup specificity of rASV's and the electrophoretic mobilities of their structural proteins were the same as those parental td viruses. The nondefectiveness of rASV's was further substantiated by the size of their genomic RNA, which was indistinguishable from that of SR-RSV-A and substantially larger than that of parental td RNA. Molecular hybridization using complementary DNA specific to the src gene of SR-RSV (cDNAsrc) showed that the RNAs of td mutants used in this study contained extensive deletions within the src gene (7 to 30% hybridization with cDNAsrc); the same probe hybridized up to 90% with RNA from two isolates of rASV. These data indicate that rASV has regained genetic information which had been deleted in the td mutants and strongly suggest that the generation of rASV involves a genetic interaction between td virus and host cell genetic information. 相似文献
15.
16.
Role of p60src kinase activity in the induction of neuroretinal cell proliferation by rous sarcoma virus. 总被引:24,自引:11,他引:13
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Expression of the src gene of Rous sarcoma virus (RSV) in chicken embryo neuroretinal (NR) cells results in morphological transformation and sustained proliferation of a normally resting cell population. We have previously reported the isolation of mutants of RSV which retain full growth-promoting activity while displaying reduced transforming properties. Two such mutants, PA101 and PA104, were used to investigate whether the p60src-associated kinase activity is required for the mitogenic function of src. A comparison of the patterns of phosphorylation of wild-type and mutant p60src revealed that the phosphorylation of tyrosine residues of p60src of PA104 was markedly reduced, whereas the relative amount of phosphotyrosine in p60src of PA101 was comparable to that of the wild-type protein. In vitro kinase activity of p60src immunoprecipitated from NR cells infected with PA101 or PA104 as measured by phosphorylation of the heavy chains of specific immunoglobulin G molecules was 1/10 that of the wild-type molecule. Moreover, when NR cells infected with mutants temperature sensitive for mitogenic capacity were maintained at a temperature either permissive or restrictive for cell growth, quantitation of kinase activity indicated that proliferation of NR cells could not be linked to the absolute level of in vitro kinase activity of p60src. Transformation of NR cells by wild-type RSV resulted in a 10-fold increase in total cellular phosphotyrosine and in the phosphorylation of tyrosine residues of a 34K protein, a possible in vivo substrate for p60src. In contrast, phosphorylation of tyrosine residues of cellular targets was markedly reduced in NR cells infected with PA101 or PA104. These results indicate that the mitogenic capacity of RSV in NR cells does not require elevated levels of p60src kinase activity. 相似文献
17.
Integration of Rous sarcoma virus DNA into chicken embryo fibroblasts: no preferred proviral acceptor site in the DNA of clones of singly infected transformed chicken cells. 总被引:3,自引:2,他引:1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We analyzed retroviral integration into a host genome by using avian sarcoma virus infection of natural target cells under conditions where secondary integration via virus spread was inhibited. This was accomplished by using the noninfectious pol- env- alpha variant of the Bryan high-titer strain of Rous sarcoma virus. A total of 12 independent Bryan high-titer Rous sarcoma virus-transformed chicken embryo fibroblast clones were obtained and mapped by using restriction endonucleases. Provirus-cell junction fragments were identified with appropriate hybridization probes. We found that expression of the viral genes could occur after proviral integration at many sites on the chicken genome and that there was no apparent preference for specific integration sites. 相似文献
18.
We analyzed the viral mRNA's present in fibroblast nonproducer clones transformed by avian erythroblastosis virus. Two size classes of mRNA (28 to 30S and 22 to 24S) were identified by solution hybridization with both complementary DNA strong stop and complementary DNA made against the unique sequences of avian erythroblastosis virus. Based upon the kinetics of hybridization with complementary DNA made against the unique sequences of avian erythroblastosis virus, we estimated that there were 400 to 500 copies of the 28 to 30S RNA per cell and 200 to 250 copies of the 22 to 24S RNA per cell. Both RNA species were packaged in the virion. In vitro translation of the 28 to 30S virion RNA yielded a 75,000-dalton protein which was the 75,000-dalton gag-related polyprotein found in avian erythroblastosis virus-transformed cells. In vitro translation of the 22 to 24S virion RNA yielded two proteins (46,000 and 48,000 daltons). This indicates that there may be two genes in avian erythroblastosis virus, one coding for the 75,000-dalton gag-related polyprotein and the second coding for the 46,000- or 48,000-dalton protein or both. 相似文献
19.
20.
Shiho Ohnishi Mariko Murata Shinji Oikawa Yusuke Hiraku Shosuke Kawanishi 《Free radical research》2013,47(6):469-478
Hydrazobenzene is carcinogenic to rats and mice and azobenzene is carcinogenic to rats. Hydrazobenzene is a metabolic intermediate of azobenzene. To clarify the mechanism of carcinogenesis by azobenzene and hydrazobenzene, we investigated DNA damage induced by hydrazobenzene, using 32P-5′-end-labeled DNA fragments obtained from the c-Ha-ras-1 proto-oncogene and the p53 tumor suppressor gene. Hydrazobenzene caused DNA damage in the presence of Cu(II). Piperidine treatment enhanced the DNA damage greatly, suggesting that hydrazobenzene caused base modification and liberation. However, azobenzene did not cause DNA damage even in the presence of Cu(II). Hydrazobenzene plus Cu(II) caused DNA damage frequently at thymine residues. Catalase and a Cu(I)-specific chelator inhibited Cu(II)-mediated DNA damage by hydrazobenzene. Typical ·OH scavengers did not inhibit the DNA damage. The main active species is probably a metal oxygen complex, such as Cu(I)-OOH. Formation of 8-oxo-7, 8-dihydro-2′-deoxyguanosine was increased by hydrazobenzene in the presence of Cu(II). Oxygen consumption and UV-Visible spectroscopic measurements have shown that hydrazobenzene is autoxidized to azobenzene with H2O2 formation. It is considered that the metal-mediated DNA damage by hydrazobenzene through H2O2 generation may be relevant for the expression of carcinogenicity of azobenzene and hydrazobenzene. 相似文献