全文获取类型
收费全文 | 748篇 |
免费 | 62篇 |
国内免费 | 2篇 |
出版年
2022年 | 8篇 |
2021年 | 12篇 |
2020年 | 7篇 |
2019年 | 6篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 11篇 |
2015年 | 18篇 |
2014年 | 16篇 |
2013年 | 34篇 |
2012年 | 44篇 |
2011年 | 43篇 |
2010年 | 17篇 |
2009年 | 19篇 |
2008年 | 66篇 |
2007年 | 60篇 |
2006年 | 52篇 |
2005年 | 58篇 |
2004年 | 51篇 |
2003年 | 43篇 |
2002年 | 36篇 |
2001年 | 10篇 |
2000年 | 6篇 |
1999年 | 10篇 |
1998年 | 15篇 |
1997年 | 14篇 |
1996年 | 5篇 |
1995年 | 9篇 |
1994年 | 8篇 |
1993年 | 12篇 |
1992年 | 12篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 9篇 |
1983年 | 4篇 |
1982年 | 13篇 |
1981年 | 9篇 |
1980年 | 4篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1970年 | 2篇 |
1964年 | 2篇 |
排序方式: 共有812条查询结果,搜索用时 15 毫秒
81.
Liu B Yang P Ye Y Zhou Y Li L Tashiro S Onodera S Ikejima T 《Free radical research》2011,45(7):835-847
Silibinin mostly has been used as hepatoprotectants, but it has other interesting activities, e.g. anti-cancer, cardial protective and brain-protective activities. A previous study demonstrated that silibinin protected amyloid β (Aβ)-induced mouse cognitive disorder by behavioural pharmacological observation. This study assessed the effect of silibinin on sodium nitroprusside (SNP)-treated rat pheochromocytoma PC12 cells. Subsequent morphologic observation, flow cytometric analysis and Western blot analysis indicated that treatment with SNP significantly induced apoptosis in PC12 cells. However, silibinin eliminated the apoptotic effect by reactive oxygen species (ROS) generation, especially hydroxyl free radical. Silibinin-induced autophagy through ROS generation when exerting a protective effect and silibinin-induced autophagy also enhanced the ROS generation since 3-methyladenine (3-MA), a specific autophagy inhibitor, decreased the ROS generation and rapamycin, an autophagy inducer, enhanced the ROS generation. Therefore, there exists a positive feedback loop between autophagy and ROS generation. Autophagy prevented SNP-induced apoptosis, since the addition of 3-MA significantly eliminated the protective effect of silibinin. This protective effect was attributed to the generation of ROS and its two downstream Ras/PI3K/NF-κB and Ras/Raf/MEK/ERK pathways. Both prevented PC12 cells from apoptosis. The PI3K/NF-κB pathway induced autophagy to protect PC12 cells, but the Raf/MEK/ERK pathway directly protected PC12 cells bypassing the autophagic effect. 相似文献
82.
Choi SS Omenetti A Syn WK Diehl AM 《The international journal of biochemistry & cell biology》2011,43(2):238-244
Repair of adult liver, like many tissues, involves the coordinated response of a number of different cell types. In adult livers, fibroblastic cells, ductular cells, inflammatory cells, and progenitor cells contribute to this process. Our studies demonstrate that the fates of such cells are dictated, at least in part, by Hedgehog, a fetal morphogenic pathway that was once thought to be active mainly during embryogenesis. Studies of injured adult human and rodent livers demonstrate that injury-related activation of the Hedgehog pathway modulates several important aspects of repair, including the growth of hepatic progenitor populations, hepatic accumulation of myofibroblasts, repair-related inflammatory responses, vascular remodeling, liver fibrosis and hepatocarcinogenesis. These findings identify the Hedgehog pathway as a potentially important target for biomarker development and therapeutic manipulation, and emphasize the need for further research to advance knowledge about how this pathway is regulated by and interacts with other signals that regulate adult liver repair. 相似文献
83.
We constructed mutant genes of Caldococcus noboribetus isocitrate dehydrogenase containing ancestral amino acid residues that were inferred using the maximal likelihood method and a composite phylogenetic tree of isocitrate dehydrogenase and 3-isopropylmalate dehydrogenase. The mutant genes were expressed in Escherichia coli and the protein products purified. Thermostabilities, reported as the half-inactivation temperatures, for the purified enzymes were determined and compared with that of the wild-type enzyme. Four of the five mutant enzymes have greater thermal stabilities than wild-type isocitrate dehydrogenase. The results are compatible with the hyperthermophilic universal ancestor (commonote) hypothesis. Incorporation of ancestral residues into a modern-day protein sequence can be used to improve protein thermostability. 相似文献
84.
Senoh M Miyoshi S Okamoto K Fouz B Amaro C Shinoda S 《Microbiology and immunology》2005,49(6):513-519
Vibrio vulnificus can be divided into two groups on the basis of pathogenesis. Group 1 is pathogenic only to humans, whereas group 2 is pathogenic to eels and occasionally to humans. Although both groups produce a 50-kDa cytotoxin-hemolysin (V. vulnificus hemolysin; VVH), the toxins are different. In the present study, the nucleotide sequence of the toxin gene (vvhA ) of strain CDC B3547 (a group 2 strain) was determined, and the deduced amino acid sequence was compared to that of strain L-180 (a group 1 strain). The nucleotide sequence of vvhA of strain CDC B3547 was about 96% identical with that of strain L-180, which results in a difference of 3 amino acid residues in the C-terminal lectin domain of VVH. Nevertheless, two primer sets for polymerase chain reaction could be designed to differentiate the toxin gene of each strain. When 27 V. vulnificus clinical isolates were tested, group 1 strains (9 strains) were shown to react only to the primers designed for vvhA of strain L-180; whereas, the gene of group 2 strains (18 strains) could be amplified with the primers for vvhA of strain CDC B3547. These findings may lead to development of a novel genetic grouping system related to the virulence potential or to the host range. 相似文献
85.
Mumps virus (MuV) has been shown to antagonize the antiviral effects of interferon (IFN) through proteasome-mediated complete degradation of STAT1 by using the viral V protein (T. Kubota et al., Biochem. Biophys. Res. Commun. 283:255-259, 2001). However, we found that MuV could inhibit IFN signaling and the generation of a subsequent antiviral state long before the complete degradation of cellular STAT1 in infected cells. In MuV-infected cells, nuclear translocation and phosphorylation of STAT1 and STAT2 tyrosine residue (Y) at 701 and 689, respectively, by IFN-beta were significantly inhibited but the phosphorylation of Jak1 and Tyk2 was not inhibited. The transiently expressed MuV V protein also inhibited IFN-beta-induced Y701-STAT1 and Y689-STAT2 phosphorylation, suggesting that the V protein could block IFN-beta-induced signal transduction without the aid of other viral components. Finally, a substitution of an alanine residue in place of a cysteine residue in the C-terminal V-unique region known to be required for STAT1 degradation and inhibition of anti-IFN signaling resulted in the loss of V protein function to inhibit the Y701-STAT1 and Y689-STAT2 phosphorylation. 相似文献
86.
Molecular and biochemical characterization of 2-hydroxyisoflavanone dehydratase. Involvement of carboxylesterase-like proteins in leguminous isoflavone biosynthesis 下载免费PDF全文
Isoflavonoids are ecophysiologically active secondary metabolites of the Leguminosae and known for health-promoting phytoestrogenic functions. Isoflavones are synthesized by 1,2-elimination of water from 2-hydroxyisoflavanones, the first intermediate with the isoflavonoid skeleton, but details of this dehydration have been unclear. We screened the extracts of repeatedly fractionated Escherichia coli expressing a Glycyrrhiza echinata cDNA library for the activity to convert a radiolabeled precursor into formononetin (7-hydroxy-4'-methoxyisoflavone), and a clone of 2-hydroxyisoflavanone dehydratase (HID) was isolated. Another HID cDNA was cloned from soybean (Glycine max), based on the sequence information in its expressed sequence tag library. Kinetic studies revealed that G. echinata HID is specific to 2,7-dihydroxy-4'-methoxyisoflavanone, while soybean HID has broader specificity to both 4'-hydroxylated and 4'-methoxylated 2-hydroxyisoflavanones, reflecting the structures of isoflavones contained in each plant species. Strikingly, HID proteins were members of a large carboxylesterase family, of which plant proteins form a monophyletic group and some are assigned defensive functions with no intrinsic catalytic activities identified. Site-directed mutagenesis with soybean HID protein suggested that the characteristic oxyanion hole and catalytic triad are essential for the dehydratase as well as the faint esterase activities. The findings, to our knowledge, represent a new example of recruitment of enzymes of primary metabolism during the molecular evolution of plant secondary metabolism. 相似文献
87.
Ishikawa S Ohtsuki S Tomita K Arihara K Itoh M 《Biological trace element research》2005,105(1-3):249-256
It is known that nonheme iron accumulates and free radicals are generated in skin exposed to ultraviolet (UV) light. Iron
ions have a role in skin photodamage by participating in the formation of reactive oxygen species. In this study, we evaluated
the effect of egg yolk phosvitin on UV-light-induced oxidative stress. Mouse dorsal skin homogenate was exposed to UVA light
in the presence or absence of ferric nitrilotriacetate, (FeNTA). Lipid peroxidation was determined by measuring thiobarbituric
acid-reactive substances (TBARS). The TBARS concentration increased with increasing FeNTA concentration and UV-light-exposure
time. In the presence of FeNTA, phosvitin more effectively inhibited in vitro lipid peroxidation than did bovine serum albumin.
According to results of electron spin resonance studies using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trapping agent, phosvitin suppressed the formation of hydroxyl radicals. These results suggest that
UV-light-induced oxidative stress can be reduced by phosvitin. 相似文献
88.
Down-regulation of osteoprotegerin production in bone marrow macrophages by macrophage colony-stimulating factor 总被引:5,自引:0,他引:5
Macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL) induce the differentiation of bone marrow macrophages (BMMs) into osteoclasts. To delineate mechanisms involved, the effect of M-CSF on the production of osteoprotegerin (OPG), decoy receptor of RANKL, in BMMs was investigated. Mouse bone marrow cells were cultured with M-CSF for 4 days and adherent cells formed were used as BMMs. BMMs were cultured with or without M-CSF, and analyzed for expression of OPG and receptor activator of NF-kappaB (RANK; receptor for RANKL) mRNAs by real-time polymerase chain reaction and secretion of OPG by enzyme-linked immunosorbent assay. BMMs expressed macrophage markers, CD115 (c-fms), Mac-1 and F4/80, and showed phagocytotic activity. In addition, BMMs expressed OPG mRNA and secreted OPG into medium. M-CSF inhibited both the OPG mRNA expression and the OPG secretion dose-dependently and reversibly. The expression of RANK mRNA was not significantly affected by M-CSF. The results showed that M-CSF suppresses the OPG production in BMMs, which may increase the sensitivity of BMMs to RANKL. 相似文献
89.
Yasunaga M Tada S Torikai-Nishikawa S Nakano Y Okada M Jakt LM Nishikawa S Chiba T Era T Nishikawa S 《Nature biotechnology》2005,23(12):1542-1550
Preparation of specific lineages at high purities from embryonic stem (ES) cells requires both selective culture conditions and markers to guide and monitor the differentiation. In this study, we distinguished definitive and visceral endoderm by using a mouse ES cell line that bears the gfp and human IL2R alpha (also known as CD25) marker genes in the goosecoid (Gsc) and Sox17 loci, respectively. This cell line allowed us to monitor the generation of Gsc+ Sox17+ definitive endoderm and Gsc- Sox17+ visceral endoderm and to define culture conditions that differentially induce definitive and visceral endoderm. By comparing the gene expression profiles of definitive and visceral endoderm, we identified seven surface molecules that are expressed differentially in the two populations. One of the seven markers, Cxcr4, to which a monoclonal antibody is available allowed us to monitor and purify the Gsc+ population from genetically unmanipulated ES cells under the condition that selects definitive endoderm. 相似文献
90.