全文获取类型
收费全文 | 599篇 |
免费 | 23篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 10篇 |
2017年 | 4篇 |
2016年 | 6篇 |
2015年 | 13篇 |
2014年 | 21篇 |
2013年 | 43篇 |
2012年 | 25篇 |
2011年 | 23篇 |
2010年 | 18篇 |
2009年 | 18篇 |
2008年 | 28篇 |
2007年 | 51篇 |
2006年 | 39篇 |
2005年 | 44篇 |
2004年 | 52篇 |
2003年 | 54篇 |
2002年 | 43篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 8篇 |
1998年 | 10篇 |
1997年 | 8篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 12篇 |
1992年 | 8篇 |
1991年 | 3篇 |
1990年 | 6篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
排序方式: 共有622条查询结果,搜索用时 31 毫秒
41.
Takada H Chen NJ Mirtsos C Suzuki S Suzuki N Wakeham A Mak TW Yeh WC 《Molecular and cellular biology》2003,23(11):4026-4033
Signaling from tumor necrosis factor receptor type 1 (TNFR1) can elicit potent inflammatory and cytotoxic responses that need to be properly regulated. It was suggested that the silencer of death domains (SODD) protein constitutively associates intracellularly with TNFR1 and inhibits the recruitment of cytoplasmic signaling proteins to TNFR1 to prevent spontaneous aggregation of the cytoplasmic death domains of TNFR1 molecules that are juxtaposed in the absence of ligand stimulation. In this study, we demonstrate that mice lacking SODD produce larger amounts of cytokines in response to in vivo TNF challenge. SODD-deficient macrophages and embryonic fibroblasts also show altered responses to TNF. TNF-induced activation of NF-kappaB is accelerated in SODD-deficient cells, but TNF-induced c-Jun N-terminal kinase activity is slightly repressed. Interestingly, the apoptotic arm of TNF signaling is not hyperresponsive in the SODD-deficient cells. Together, these results suggest that SODD is critical for the regulation of TNF signaling. 相似文献
42.
Interactions between cells and between tissues are importantin the development and morphogenesis of higher plants. Attemptsto characterize the role of the cell wall in such interactionshave benefited from the use of carrot (Daucus carota L.) culturedcells in vitro as a model system. The development of carrotcells in culture can be divided into three processes: the acquisitionof embryogenic competence; the development of the embryo; andthe maturation and dormancy of the embryo. Induction of non-embryogeniccallus is accompanied by weakened intercellular attachment,decreased levels of endogenous ABA and a decrease in responsivenessto exogenous ABA. Cell wall polysaccharides are known to beinvolved in various developmental and morphogenetic events.In carrot cultured cells, possible roles in intercellular attachmenthave been proposed for arabinan and xylose in the neutral sugarregions of pectins, and various extracellular proteins havebeen shown to be involved in somatic embryogenesis in vitro.Some of these proteins are also present around and/or in zygoticembryos, possibly being involved in the formation and functionsof zygotic embryos and seeds. A 57-kDa extracellular solubleglycoprotein that binds to insulin-like peptides and an 18-kDaextracellular insoluble cystatin that inhibits the proteinasesof germinating seeds of carrot might be involved in cellularsignal transduction and inter-tissue interaction, respectively,in carrot seeds.
1 Recipient of the JSPP Young Investigator Award, 1997 相似文献
43.
Seiji Iwama Masaki Segawa Shinobu Fujii Kiyoshi Ikeda Shigeo Katsumura 《Bioorganic & medicinal chemistry letters》1998,8(24):781-3498
All stereoisomers of N-acyl-4,5-disubstituted oxazolidinone phospholipid analogs were synthesized by regio and stereoselective epoxide ring opening accompanied by introduction of an amino group. The (4R,5S)-derivative showed stronger inhibitory activity toward type II phospholipase A2 than the 4-substituted oxazolidinone phospholipid analog previously reported. 相似文献
44.
Yayoi Sato Hiromitsu Hara Toshiaki Okuno Naoko Ozaki Shinobu Suzuki Takehiko Yokomizo Tsuneyasu Kaisho Hiroki Yoshida 《Biochemical and biophysical research communications》2014
IL-27 is a heterodimeric cytokine that regulates both innate and adaptive immunity. The immunosuppressive effect of IL-27 largely depends on induction of IL-10-producing Tr1 cells. To date, however, effects of IL-27 on regulation of immune responses via mediators other than cytokines remain poorly understood. To address this issue, we examined immunoregulatory effects of conditional medium of bone marrow-derived macrophages (BMDMs) from WSX-1 (IL-27Rα)-deficient mice and found enhanced IFN-γ and IL-17A secretion by CD4+ T cells as compared with that of control BMDMs. We then found that PGE2 production and COX-2 expression by BMDMs from WSX-1-deficient mice was increased compared to control macrophages in response to LPS. The enhanced production of IFN-γ and IL-17A was abolished by EP2 and EP4 antagonists, demonstrating PGE2 was responsible for enhanced cytokine production. Murine WSX-1-expressing Raw264.7 cells (mWSX-1-Raw264.7) showed phosphorylation of both STAT1 and STAT3 in response to IL-27 and produced less amounts of PGE2 and COX-2 compared to parental RAW264.7 cells. STAT1 knockdown in parental RAW264.7 cells and STAT1-deficiency in BMDMs showed higher COX-2 expression than their respective control cells. Collectively, our result indicated that IL-27/WSX-1 regulated PGE2 secretion via STAT1–COX-2 pathway in macrophages and affected helper T cell response in a PGE2-mediated fashion. 相似文献
45.
Masanori A. Murayama Shigeru Kakuta Takumi Maruhashi Kenji Shimizu Akimasa Seno Sachiko Kubo Nozomi Sato Shinobu Saijo Masahira Hattori Yoichiro Iwakura 《Biochemical and biophysical research communications》2014
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease exhibited most commonly in joints. We found that the expression of C1qtnf3, which encodes C1q/TNF-related protein 3 (CTRP3), was highly increased in two mouse RA models with different etiology. To elucidate the pathogenic roles of CTRP3 in the development of arthritis, we generated C1qtnf3−/− mice and examined the development of collagen-induced arthritis in these mice. We found that the incidence and severity score was higher in C1qtnf3−/− mice compared with wild-type (WT) mice. Histopathology of the joints was also more severe in C1qtnf3−/− mice. The levels of antibodies against type II collagen and pro-inflammatory cytokine mRNAs in C1qtnf3−/− mice were higher than WT mice. These observations indicate that CTRP3 plays an important role in the development of autoimmune arthritis, suggesting CTRP3 as a possible medicine to treat RA. 相似文献
46.
Jung-Soo Kim Kosuke Okamoto Shinobu Arima Bruce K Rubin 《Journal of applied physiology》2006,101(2):486-491
Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are neurotransmitters involved in the regulation of bronchial and pulmonary vascular tone. Published studies of the effects of VIP on airway mucus secretion have yielded conflicting results. The purpose of this study was to determine the effect of VIP on mucus secretion in the ferret trachea and if this effect was influenced by NO. We used a sandwich enzyme-linked lectin assay to measure mucin secretion and a turbidimetric assay to measure lysozyme (serous cell) secretion from ferret tracheal segments. VIP (10(-7) M) increased mucin secretion over 2 h. VIP (10(-9) to 10(-5) M) stimulated mucin secretion in a dose-dependent fashion. VIP-induced mucin secretion was partially blocked by a VIP receptor antagonist (a chimeric VIP-pituitary adenylate cyclase-activating peptide analog, VIP receptor antagonist) at a 10-fold excess concentration. At all concentrations tested, neither NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, nor S-nitroso-N-acetyl-penicillamine, an NO donor, had any significant effect on constitutive or VIP-induced mucus secretion. We conclude that VIP-stimulated mucin and lysozyme secretion was both time dependent and dose dependent and that NO neither stimulates nor inhibits mucus secretion in the ferret trachea. 相似文献
47.
48.
Aoki Y Ono H Yasuo S Masuda T Yoshimura T Ebihara S Iigo M Yanagisawa T 《Zoological science》2007,24(7):686-692
A cDNA encoding prepro-thyrotropin-relaesing hormone (ppTRH) in chicken (Gallus gallus) was isolated and the sites of expression in the brain were determined. The chicken ppTRH cDNA encodes 260 amino acids, including four TRH progenitor sequences (-Lys/Arg-Arg-Gln-His-Pro-Gly-Lys/Arg-Arg-). It is interesting to note that chicken ppTRH harbors four TRH progenitor-like sequences. According to the hydropathy profile of chicken ppTRH, not only the TRH progenitor sequences but also the TRH progenitor-like sequences are localized in hydrophilic regions. The TRH progenitor-like sequences might be related to structural conservation in the evolution of ppTRH, although they cannot be processed into TRH due to the mutation of several amino acids. According to the alignment of the deduced amino-acid sequences of known vertebrate ppTRHs and the molecular phylogenetic tree we constructed, we speculate on the molecular evolution of ppTRH in vertebrates. In situ hybridization demonstrated experession of the ppTRH gene in the nucleus preopticus periventricularis, nucleus preopticus medialis, regio lateralis hypothalami, paraventricular nucleus, nucleus periventricularis hypothalami, and nucleus ventromedialis hypothalami in the chicken brain. 相似文献
49.
Yasuo S Watanabe M Iigo M Nakamura TJ Watanabe T Takagi T Ono H Ebihara S Yoshimura T 《American journal of physiology. Regulatory, integrative and comparative physiology》2007,292(3):R1315-R1319
The molecular basis of seasonal or nonseasonal breeding remains unknown. Although laboratory rats are generally regarded as photoperiod-insensitive species, the testicular weight of the Fischer 344 (F344) strain responds to photoperiod. Recently, it was clarified that photoperiodic regulation of type 2 iodothyronine deiodinase (Dio2) in the mediobasal hypothalamus (MBH) is critical in photoperiodic gonadal regulation. Strain-dependent differences in photoperiod sensitivity may now provide the opportunity to address the regulatory mechanism of seasonality by studying Dio2 expression. Therefore, in the present study, we examined the effect of photoperiod on Dio2 expression in photoperiod-sensitive F344 and photoperiod-insensitive Wistar rats. A statistically significant difference was observed between short and long days in terms of testicular weight and Dio2 expression in the F344 strain, while no difference was observed in the Wistar strain. These results suggest that differential responses of the Dio2 gene to photoperiod may determine the strain-dependent differences in photoperiod sensitivity in laboratory rats. 相似文献
50.
Shintaro Iwashita Takehiro Suzuki Takeshi Yasuda Kentaro Nakashima Taiichi Sakamoto Toshiyuki Kohno Ichiro Takahashi Takayasu Kobayashi Yoshiko Ohno-Iwashita Shinobu Imajoh-Ohmi Si-Young Song Naoshi Dohmae 《Bioscience reports》2015,35(4)
The BCNT (Bucentaur) superfamily is classified by an uncharacteristic conserved sequence of ∼80 amino acids (aa) at the C-terminus, BCNT-C (the conserved C-terminal region of Bcnt/Cfdp1). Whereas the yeast Swc5 and Drosophila Yeti homologues play crucial roles in chromatin remodelling organization, mammalian Bcnt/Cfdp1 (craniofacial developmental protein 1) remains poorly understood. The protein, which lacks cysteine, is largely disordered and comprises an acidic N-terminal region, a lysine/glutamic acid/proline-rich 40 aa sequence and BCNT-C. It shows complex mobility on SDS/PAGE at ∼50 kDa, whereas its calculated molecular mass is ∼33 kDa. To characterize this mobility discrepancy and the effects of post-translational modifications (PTMs), we expressed various deleted His–Bcnt in E. coli and HEK cells and found that an acidic stretch in the N-terminal region is a main cause of the gel shift. Exogenous BCNT/CFDP1 constitutively expressed in HEK clones appears as a doublet at 49 and 47 kDa, slower than the protein expressed in Escherichia coli but faster than the endogenous protein on SDS/PAGE. Among seven in vivo phosphorylation sites, Ser250, which resides in a region between disordered and ordered regions in BCNT-C, is heavily phosphorylated and detected predominantly in the 49 kDa band. Together with experiments involving treatment with phosphatases and Ser250 substitutions, the results indicate that the complex behaviour of Bcnt/Cfdp1 on SDS/PAGE is caused mainly by an acidic stretch in the N-terminal region and Ser250 phosphorylation in BCNT-C. Furthermore, Bcnt/Cfdp1 is acetylated in vitro by CREB-binding protein (CBP) and four lysine residues including Lys268 in BCNT-C are also acetylated in vivo, revealing a protein regulated at multiple levels. 相似文献