全文获取类型
收费全文 | 169篇 |
免费 | 8篇 |
专业分类
177篇 |
出版年
2023年 | 3篇 |
2022年 | 9篇 |
2021年 | 6篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 10篇 |
2014年 | 7篇 |
2013年 | 15篇 |
2012年 | 13篇 |
2011年 | 17篇 |
2010年 | 6篇 |
2009年 | 5篇 |
2008年 | 10篇 |
2007年 | 6篇 |
2006年 | 9篇 |
2005年 | 5篇 |
2004年 | 9篇 |
2003年 | 5篇 |
2002年 | 4篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有177条查询结果,搜索用时 0 毫秒
31.
Miho Chikazawa Natsuki Otaki Takahiro Shibata Takehiko Yasueda Tsukasa Matsuda Koji Uchida 《PloS one》2013,8(7)
Milk fat globule epidermal growth factor 8 (MFG-E8) is a protein that binds to apoptotic cells by recognizing phosphatidylserine and enhances the engulfment of apoptotic cells by macrophages. Many apoptotic cells are left unengulfed in the germinal centers of the spleen in the MFG-E8-deficient (MFG-E8−/−) mice, and these mice develop an autoimmune disease resembling human systemic lupus erythematosus. We found that the MFG-E8 deficiency was accompanied by the increased production of immunoglobulins. Further Western blot and ELISA analyses validated the increase in the IgM levels in the MFG-E8−/− mice. It was also revealed that the sera from the MFG-E8−/− mice cross-reacted with oxidation-specific epitopes generated upon incubation of serum albumin with the peroxidized lipids. Among the modified proteins with several unsaturated aldehydes of chain lengths varying from three to nine carbons, the MFG-E8−/− mice sera exclusively cross-reacted with the protein-bound 4-oxo-2-nonenal (ONE), a highly reactive aldehyde originating from the peroxidation of ω6 polyunsaturated fatty acids. In addition, the IgM monoclonal antibodies (mAbs) that selectively cross-reacted with the ONE-modified proteins were generated from the MFG-E8−/− mice. A subset of the ONE-specific IgM mAbs significantly recognized the late apoptotic and necrotic cells and enhanced the phagocytosis by macrophages. These data demonstrate that the impairment of the phagocytic clearance of apoptotic cells through MFG-E8 can lead to the generation of natural antibodies, which may play a critical role in removing multiple damage-associated molecules, including oxidation-specific epitopes and late apoptotic/necrotic cells. 相似文献
32.
Nei T Urano S Motoi N Takizawa J Kaneko C Kanazawa H Tazawa R Nakagaki K Akagawa KS Akasaka K Ichiwata T Azuma A Nakata K 《American journal of physiology. Lung cellular and molecular physiology》2012,302(9):L959-L964
The granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody (GMAb) is the causative agent underlying autoimmune pulmonary alveolar proteinosis (aPAP). It consists primarily of the IgG isotype. At present, information on other isotypes of the autoantibody is limited. We detected serum the IgM isotype of GMAb (IgM-GMAb) in more than 80% of patients with aPAP and 22% of healthy subjects, suggesting that a continuous antigen pressure may be present in most patients. Levels of the IgM isotype were weakly correlated with IgG-GMAb levels but not IgA-GMAb, suggesting that its production may be associated with that of IgG-GMAb. The mean binding avidity to GM-CSF of the IgM isotype was 100-fold lower than the IgG-GMAb isotype, whereas the IC(50) value for neutralizing capacity was 20,000-fold higher than that of IgG-GMAb, indicating that IgM-GMAb is only a very weak neutralizer of GM-CSF. In bronchoalveolar lavage fluid from nine patients, IgG-GMAb was consistently detected, but IgM-GMAb was under the detection limit in most patients, confirming that IgM-GMAb is functionally a bystander in the pathogenesis of aPAP. It rather may be involved in the mechanism for development of IgG-GMAb in vivo. 相似文献
33.
Yasuhiro Moriwaki Kiyoko Takada Toshinori Nagasaki Natsuki Kubo Tomohiro Ishii Kazuaki Kose Taihei Kageyama Shoutaro Tsuji Koichiro Kawashima Hidemi Misawa 《PloS one》2015,10(10)
Background
SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Moreover, although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied, and the pathophysiological control of SLURP1 expression in keratinocytes is largely unknown.Objectives
Our aim was to examine the involvement of SLURP1 in the pathophysiology of psoriasis using an imiquimod (IMQ)-induced psoriasis model mice and normal human epidermal keratinocytes (NHEKs).Results
SLURP1 expression was up-regulated in the skin of IMQ-induced psoriasis model mice. In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-α, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines. The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3. Because IL-22 induces production of antimicrobial proteins in epithelial cells, the antibacterial activity of SLURP1 was assessed against Staphylococcus aureus (S. aureus), which is known to be associated with disease severity in psoriasis. SLURP1 significantly suppressed the growth of S. aureus.Conclusions
These results indicate SLURP1 participates in pathophysiology of psoriasis by regulating keratinocyte proliferation and differentiation, and by suppressing the growth of S. aureus. 相似文献34.
Background
α-Synuclein is a Parkinson's-disease-related protein. It forms aggregates in vivo, and these aggregates cause cell cytotoxicity. Aggregation inhibitors are expected to reduce α-synuclein cytotoxicity, and an aggregation accelerator has recently been reported to reduce α-synuclein cytotoxicity. Therefore, amyloid aggregation modulating ligands are expected to serve as therapeutic medicines. 相似文献35.
36.
Therapeutic effect of intra‐articular injection of ribbon‐type decoy oligonucleotides for hypoxia inducible factor‐1 on joint contracture in an immobilized knee animal model 下载免费PDF全文
37.
38.
39.
Ki-Seok Yoon Yukiko Sakai Natsuki Tsukada Kiyoshi Fujisawa & Hirofumi Nishihara 《FEMS microbiology letters》2009,290(1):114-120
Membrane-bound [NiFe]-hydrogenase from Hydrogenophaga sp. AH-24 was purified to homogeneity. The molecular weight was estimated as 100±10 kDa, consisting of two different subunits (62 and 37 kDa). The optimal pH values for H2 oxidation and evolution were 8.0 and 4.0, respectively, and the activity ratio (H2 oxidation/H2 evolution) was 1.61 × 102 at pH 7.0. The optimal temperature was 75 °C. The enzyme was quite stable under air atmosphere (the half-life of activity was c . 48 h at 4 °C), which should be important to function in the aerobic habitat of the strain. The enzyme showed high thermal stability under anaerobic conditions, which retained full activity for over 5 h at 50 °C. The activity increased up to 2.5-fold during incubation at 50 °C under H2 . Using methylene blue as an electron acceptor, the kinetic constants of the purified membrane-bound homogenase (MBH) were V max =336 U mg−1 , k cat =560 s−1 , and k cat / K m =2.24 × 107 M−1 s−1 . The MBH exhibited prominent electron paramagnetic resonance signals originating from [3Fe–4S]+ and [4Fe–4S]+ clusters. On the other hand, signals originating from Ni of the active center were very weak, as observed in other oxygen-stable hydrogenases from aerobic H2 -oxidizing bacteria. This is the first report of catalytic and biochemical characterization of the respiratory MBH from Hydrogenophaga . 相似文献
40.
Mizuho Sato Alato Okuno Kazunori Suzuki Natsuki Ohsawa Eiichi Inoue Yuji Miyaguchi 《Bioscience, biotechnology, and biochemistry》2013,77(9):1756-1765
ABSTRACTDepressive disorders are partly caused by chronic inflammation through the kynurenine (KYN) pathway. Preventive intervention using anti-inflammatory reagents may be beneficial for alleviating the risk of depression. In this study, we focused on the Japanese local citrus plant, Citrus tumida hort. ex Tanaka (C. tumida; CT), which contains flavonoids such as hesperidin that have anti-inflammatory actions. The dietary intake of 5% immature peels of CT fruits slightly increased stress resilience in a subchronic and mild social defeat (sCSDS) model in mice. Moreover, the dietary intake of 0.1% hesperidin significantly increased stress resilience and suppressed KYN levels in the hippocampus and prefrontal cortex in these mice. In addition, KYN levels in the hippocampus and prefrontal cortex were significantly correlated with the susceptibility to stress. In conclusion, these results suggest that dietary hesperidin increases stress resilience by suppressing the augmentation of KYN signaling under sCSDS. 相似文献