全文获取类型
收费全文 | 961篇 |
免费 | 51篇 |
出版年
2023年 | 6篇 |
2022年 | 4篇 |
2021年 | 7篇 |
2020年 | 6篇 |
2019年 | 16篇 |
2018年 | 9篇 |
2017年 | 12篇 |
2016年 | 16篇 |
2015年 | 30篇 |
2014年 | 40篇 |
2013年 | 56篇 |
2012年 | 49篇 |
2011年 | 52篇 |
2010年 | 35篇 |
2009年 | 26篇 |
2008年 | 44篇 |
2007年 | 48篇 |
2006年 | 44篇 |
2005年 | 47篇 |
2004年 | 45篇 |
2003年 | 48篇 |
2002年 | 37篇 |
2001年 | 40篇 |
2000年 | 49篇 |
1999年 | 22篇 |
1998年 | 9篇 |
1997年 | 11篇 |
1996年 | 10篇 |
1995年 | 6篇 |
1994年 | 8篇 |
1993年 | 10篇 |
1992年 | 29篇 |
1991年 | 21篇 |
1990年 | 16篇 |
1989年 | 8篇 |
1988年 | 15篇 |
1987年 | 11篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 12篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1976年 | 3篇 |
1974年 | 3篇 |
1970年 | 2篇 |
1967年 | 2篇 |
排序方式: 共有1012条查询结果,搜索用时 31 毫秒
1.
N Fatma D P Singh T Shinohara L T Chylack 《The Journal of biological chemistry》2001,276(52):48899-48907
Antioxidant protein 2 (AOP2), a member of the newly defined family of thiol-specific antioxidant proteins, has been shown to remove H(2)O(2) and protect proteins and DNA from oxidative stress. Here we report that LEDGF is one of the regulatory factors for the AOP2 gene. We found that LEDGF bound to the heat shock element and to stress-related elements in the AOP2 promoter. It trans-activated expression of AOP2-CAT in COS-7 cells and lens epithelial cells overexpressing LEDGF. Mutations in the heat shock element and stress-related elements of the AOP2 promoter reduced LEDGF-dependent trans-activation. Lens epithelial cells showed a higher level of AOP2 mRNA in the presence of LEDGF. Cells overexpressing LEDGF exhibited a higher level of AOP2 protein, the level of which was directly related to the increase in cellular protection. Thus, LEDGF, by activating the AOP2 gene, protected and enhanced the survival of cells under oxidative stress. 相似文献
2.
The upper limb nerves of 8 human embryos (Carnegie stages 13-21) were studied by reconstruction. In stage 13, upper limb nerves (C5-T1) extended from the spinal cord. In stage 14, these nerves united to form the nascent brachial plexus. In stages 16 and 17, the median nerve, the radial nerve and the ulnar nerve entered into the hand plate. In stages 20 and 21, the upper limb nerves were observed in an orientation and arrangement similar to those in the adult. 相似文献
3.
V K Singh H K Kalra K Yamaki T Abe L A Donoso T Shinohara 《Journal of immunology (Baltimore, Md. : 1950)》1990,144(4):1282-1287
S-Antigen (S-Ag) is a well characterized 45,000 m.w. photoreceptor cell protein. When injected into susceptible animal species, including primates, it induces an experimental autoimmune uveitis, a predominantly T cell-mediated autoimmune disease of the retina and uveal tract of the eye, and of the pineal gland. In this study we found an amino acid sequence homology between a uveitopathogenic site of S-Ag, several viral proteins and one additional nonviral protein. An experimental autoimmune uveitis and pinealitis was induced in Lewis rats with these different synthetic peptides, corresponding to the amino sequence of hepatitis B virus DNA polymerase, gag-pol polyprotein of Baboon endogenous virus and gag-pol polyprotein of AKV murine leukemia virus and potato proteinase inhibitor IIa, which contain three or more consecutive amino acids identical to peptide M in S-Ag. Lymph node cells from rats immunized with either peptide M or the different synthetic peptides showed a significant degree of cross-reaction. Mononuclear cells from monkeys (Macaca fascicularis) immunized with peptide M also showed significant proliferation when incubated with either peptide M or synthetic peptides as measured by in vitro lymphocyte mitogenesis assay using [3H]TdR. Based on our findings we conclude that a viral infection may sensitize the mononuclear cells that can cross-react with self proteins by a mechanism termed molecular mimicry. Tissue injury from the resultant autoantigenic event can take place in the absence of the infectious virus that initiated the immune response. 相似文献
4.
The golden hamster ovarian bursa was studied by light and electron microscopy to clarify the process of its complete closure and the development of lymphatics that leads to morphogenesis of stomata. The results were as follows. 1) The bursa completely closed at 9 days of age primarily due to development of the mesotubarium superius. 2) With the closure, the ovary and bursa became closely apposed, and most of the original bursal cavity disappeared. 3) Between 9 and 12 days of age U-shaped folds of the bursal mesothelium began to invade the connective tissue of the bursa. 4) Widening of the internal angle of the U-shaped folds contributed to reappearance of the bursal cavity, and thus separation of the bursa from the ovary. It also contributed to future geometrical proximity of lymphatics to the cavity of the bursa. 5) The separation of the bursa from the ovary began as early as 12 days of age in the cephalic half of the bursa. It occurred remarkably late in the caudal half. Juxtaposition of the window portion of the bursa to the ovary remained in some adult animals. 6) Development of lymphatics in the cephalic half of the bursa was divided into two stages, before and after days 21-24 of life. In the first stage, lymphatics grew in the submesothelial connective tissue, and the framework of lymphatics was formed. In the second stage, lymphatics extended small branches to form the submesothelial plexus or lymphatic lacuna. 7) Intercellular junctions between contiguous lymphatic endothelial cells were mostly tight and desmosomelike. Open junctions were, if they occurred at all, rare. (8) A smooth-surfaced area lined with the lymphatic endothelium was found in the bursa on day 27 of life, before the initiation of ovulation. Valvelike stomal orifices were absent before the initiation of ovulation and extremely rare even after the first ovulation. They were commonly present in the bursae after the fourth ovulation, however. The process of complete closure of the ovarian bursa is very complex and may be related to the later development of the bursal mesothelium and lymphatics. Some liplike stomal orifices are of purely developmental origin. However, all valvelike stomal orifices are assumed to be formed as a result of damage to the bursal mesothelium, as well as to the submesothelial connective tissue and lymphatics, by repetition of ovulation. It is possible that liplike stomal orifices may be formed in the process of repairing the damage. 相似文献
5.
6.
Experimental autoimmune uveitis (EAU) is caused by the immunization of microgram amounts of a soluble retinal protein, known as S-antigen, in susceptible animal strains including primates. The disease serves as an animal model of ocular inflammation. We induced EAU and pinealitis in Lewis rats with small synthetic peptides, corresponding to the amino acid sequence in Escherichia coli protein, which contains six consecutive amino acids identical to a uveitopathogenic site in human S-antigen (peptide M). EAU and pinealitis induced in rats by synthetic peptide derived from E. coli was indistinguishable from those induced by native S-antigen or other uveitopathogenic synthetic peptides corresponding to the amino acid sequence of S-antigen. Furthermore, lymph node cells from animals immunized with either peptide M or peptide derived from E. coli protein showed significant proliferation in the presence of either peptide when tested in vitro for lymphocyte mitogenesis using [3H]thymidine. Thus, molecular mimicry, a process by which an immune response directed against a nonself protein cross-reacts with a normal host protein, may play a role in autoimmunity. 相似文献
7.
Experimental autoimmune uveitis (EAU) serves as an animal model of ocular inflammation. The disease is caused by the immunization of microgram amounts of a soluble retinal protein, designated S-antigen, in susceptible animal strains, including primates. We induced EAU and experimental autoimmune pinealitis (EAP) in Lewis rats with a small synthetic peptide corresponding to amino acid positions 106-121 in yeast histone H3. This peptide contains five consecutive amino acids identical to a uveitopathogenic site (peptide M) in human S-antigen. Lymph node or mononuclear cells from different species of animals immunized either with histone H3 or with peptide M showed significant cross-reaction as measured by in vitro lymphocyte mitogenesis assay using [3H]thymidine. Also, we adoptively transferred the EAU and EAP in naive rats by immune lymph node cells. These findings support the fact that selected bacterial, viral, or fungal proteins with amino acid sequence homologies to normal retinal proteins are uveitopathogenic and, as such, provide a basis for autoimmune inflammatory diseases. 相似文献
8.
Expression and processing of cyanobacterial Mn-stabilizing protein in Escherichia coli 总被引:1,自引:0,他引:1
The woxA gene of cyanobacterium Anacystis nidulans R2, which encodes the precursor of the Mn-stabilizing protein involved in photosynthetic water oxidation, was found to be expressed in Escherichia coli. The 30-kDa expression product was indistinguishable from the authentic mature protein on SDS/PAGE. Upon fractionation of E. coli cells, the expression product was co-precipitated with the membrane fraction, which is consistent with the water-insoluble nature of the authentic mature protein. Analysis of the amino-terminal amino acid sequence of the product revealed that it is identical to the sequence from the 28th residue of the precursor, indicating that the precursor is processed in E. coli. The expression product was digested by trypsinization of E. coli spheroplasts, but not by that of intact cells. This observation suggests that the product is secreted from the cytoplasmic membrane, but not from the outer membrane. The occurrence of both processing and secretion suggests that a signal peptidase of E. coli can recognize the structure for translocation across the thylakoid membrane. Comparison of the signal sequence and the presequence of sweet potato sporamin A suggests that the processing enzymes of the thylakoid membrane and endoplasmic reticulum possess a common substrate specificity. 相似文献
9.
Rat pineal S-antigen: sequence analysis reveals presence of alpha-transducin homologous sequence 总被引:2,自引:0,他引:2
T Abe K Yamaki M Tsuda V K Singh S Suzuki R McKinnon D C Klein L A Donoso T Shinohara 《FEBS letters》1989,247(2):307-311
S-antigen (S-Ag) is a soluble, highly antigenic protein, the administration of which induces autoimmune uveitis. This protein is found in the retina and pineal. Retinal S-Ag from three species has been sequenced. In this study rat pineal S-Ag was sequenced. Clones were isolated from a rat pineal lambda gt11 cDNA library by probing with a 300 bp fragment of mouse retinal S-Ag cDNA containing the 5'-coding region. The largest clone isolated (RPS-118; 1364 bp) contained the entire coding sequence. Comparison of the rat pineal and mouse retinal S-Ag nucleotide sequences indicated a high homology (95%). The deduced amino acid sequence was found to contain 403 residues (congruent to 44 992 Da). Comparison of the rat pineal and mouse retinal S-Ag amino acid sequences also revealed high homology (97%). The similarity of both the nucleotide and amino acid sequences of rat pineal and mouse retinal S-Ag indicates that expression of the S-Ag gene in both tissues is similar. Further analysis of the rat pineal S-Ag sequence indicated that it contained essentially the same major uveitopathogenic region of S-Ag present in bovine retina; minor uveitopathogenic sites were somewhat different. As is true of retinal S-Ag, rat pineal S-Ag contains the same consensus phosphoryl-binding site present in many GTP/GDP-binding proteins and a homologous sequence found in the C-terminus of alpha-transducin. These sequences may play a role in the action of pineal S-Ag in transmembrane signal transduction. 相似文献
10.
M Miwa M Tsuda Y Kurashima H Hara Y Tanaka K Shinohara 《Biochemical and biophysical research communications》1989,159(2):373-378
Thioproline (Thiazolidine-4-carboxylic acid) and proline were nitrosated by stimulated mouse macrophages in vitro. A macrophage cell line (J774.1, 1.0 x 10(6)/well, 1 ml) was incubated with Escherichia coli lipopolysaccharide, interferon-gamma and thioproline (5 mM) or proline (5 mM). After 72 hr incubation at 37 degrees C, 4 microM N-nitrosothioproline was produced. The amount of N-nitrosoproline was much lower than that of N-nitrosothioproline. Thioproline and proline inhibited the formation of carcinogenic N-nitrosomorpholine. N-nitrosothioproline and N-nitrosoproline are found as major N-nitroso compounds in human urine. Macrophage mediated N-nitrosation may contribute to the formation of these N-nitrosamino acids in the human body. 相似文献