全文获取类型
收费全文 | 488篇 |
免费 | 27篇 |
出版年
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 3篇 |
2016年 | 6篇 |
2015年 | 9篇 |
2014年 | 17篇 |
2013年 | 36篇 |
2012年 | 20篇 |
2011年 | 18篇 |
2010年 | 13篇 |
2009年 | 13篇 |
2008年 | 24篇 |
2007年 | 24篇 |
2006年 | 28篇 |
2005年 | 32篇 |
2004年 | 33篇 |
2003年 | 29篇 |
2002年 | 26篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 12篇 |
1998年 | 6篇 |
1997年 | 8篇 |
1996年 | 2篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 8篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 8篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 4篇 |
1981年 | 8篇 |
1980年 | 8篇 |
1979年 | 4篇 |
1978年 | 10篇 |
1977年 | 4篇 |
1976年 | 10篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1970年 | 3篇 |
排序方式: 共有515条查询结果,搜索用时 140 毫秒
61.
Kontani K Kajino K Huangi CL Fujino S Taguchi O Yamauchi A Yokomise H Ogasawara K 《Cancer immunology, immunotherapy : CII》2006,55(5):579-587
Since immunity is generally suppressed by immunoregulatory factors, such as transforming growth factor-beta (TGF-β), interleukin (IL)-10, and vascular endothelial growth factor (VEGF), produced by tumor cells or stromal cells surrounding tumor cells, various kinds of cancer immunotherapy mostly fail to elicit potent antitumor immunity. Herein, we tested whether neutralization of TGF-β can elicit strong antitumor immune responses and tumor regression in tumor-bearing mice. A plasmid DNA, pcDNA-sTGFβR/huIg, encoding a fusion protein consisting of the extracellular domain of TGF-β type II receptor (TGFβRII) and the Fc portion of human IgG heavy chain, was injected through different routes into B6 mice carrying established tumors of E.G7 cells, which consist of the poorly immunogenic tumor cells EL4, transfected with the ovalbumin (OVA) gene. The frequency of OVA-specific cytotoxic T lymphocytes (CTL), in the treated mice. increased resulting in the tumor eradication and relapse-free survival in around 70% of the E.G7-bearing mice. In contrast, administration of mock DNA into E.G7-bearing mice did not elicit tumor-specific immune responses. Therefore, administration of DNA encoding TGFβRII allowed tumor-bearing hosts to elicit sufficiently potent antitumor immune responses without requirement of further active antigen-immunization. This strategy seems to be applicable to clinical therapy against cancer, because it is low-cost, safe, and easy to manipulate. 相似文献
62.
63.
Itoh S Saito T Hirata M Ushita M Ikeda T Woodgett JR Algül H Schmid RM Chung UI Kawaguchi H 《The Journal of biological chemistry》2012,287(35):29227-29236
64.
Mao Nagasawa Yumi Ogino Koji Kurata Tsuyoshi Otsuka Jyunki Yoshida Shozo Tomonaga Mitsuhiro Furuse 《Amino acids》2012,43(5):2101-2111
While abnormalities in monoamine metabolism have been investigated heavily per potential roles in the mechanisms of depression, the contribution of amino acid metabolism in the brain remains not well understood. In additional, roles of the hypothalamus–pituitary–adrenal axis in stress-regulation mechanisms have been of much focus, while the contribution of central amino acid metabolism to these mechanisms has not been well appreciated. Therefore, whether depression-like states affect amino acid metabolism and their potential roles on stress-regulatory mechanisms were investigated by comparing Wistar Kyoto rats, which display depression-like behaviors and stress vulnerability, to control Wistar rats. Brain amino acid metabolism in Wistar Kyoto rats was greatly different from normal Wistar rats, with special reference to lower cystathionine and serine levels. In addition, Wistar Kyoto rats demonstrated abnormality in dopamine metabolism compared with Wistar rats. In the case of stress response, amino acid levels having a sedative and/or hypnotic effect were constant in the brain of Wistar Kyoto rats, though these amino acid levels were reduced in Wistar rats under a stressful condition. These results suggest that the abnormal amino acid metabolism may induce depression-like behaviors and stress vulnerability in Wistar Kyoto rats. Therefore, we hypothesized that abnormalities in amino acid and monoamine metabolism may induce depression, and amino acid metabolism in the brain may be related to stress vulnerability. 相似文献
65.
66.
67.
Baudino L Shinohara Y Nimmerjahn F Furukawa J Nakata M Martínez-Soria E Petry F Ravetch JV Nishimura S Izui S 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(9):6664-6669
Replacement of aspartic acid by alanine at position 265 (D265A) in mouse IgG1 results in a complete loss of interaction between this isotype and low-affinity IgG Fc receptors (Fc gammaRIIB and Fc gammaRIII). However, it has not yet been defined whether the D265A substitution could exhibit similar effects on the interaction with two other Fc gammaR (Fc gammaRI and Fc gammaRIV) and on the activation of complement. To address this question, 34-3C anti-RBC IgG2a and IgG2b switch variants bearing the D265A mutation were generated, and their effector functions and in vivo pathogenicity were compared with those of the respective wild-type Abs. The introduction of the D265A mutation almost completely abolished the binding of 34-3C IgG2a and IgG2b to all four classes of Fc gammaR and the activation of complement. Consequently, these mutants were hardly pathogenic. Although oligosaccharide side chains of these mutants were found to contain higher levels of sialic acids than those of wild-type Abs, the analysis of enzymatically desialylated D265A variants ruled out the possibility that very poor Fc-associated effector functions of the D265A mutants were due to an increased level of the mutant Fc sialylation. Thus, our results demonstrate that aspartic acid at position 265 is a residue critically implicated in triggering the Fc-associated effector functions of IgG, probably by defining a crucial three-dimensional structure of the Fc region. 相似文献
68.
Baudino L Nimmerjahn F Shinohara Y Furukawa J Petry F Verbeek JS Nishimura S Ravetch JV Izui S 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(6):4107-4112
Four murine IgG subclasses display markedly different Fc-associated effector functions because of their differential binding to three activating IgG Fc receptors (FcgammaRI, FcgammaRIII, and FcgammaRIV) and C1q. Previous analysis of IgG subclass switch variants of 34-3C anti-RBC monoclonal autoantibodies revealed that the IgG1 subclass, which binds only to FcgammaRIII and fails to activate complement, displayed the poorest pathogenic potential. This could be related to the presence of a three amino acid deletion at positions 233-235 in the CH2 domain uniquely found in this subclass. To address this question, IgG1 insertion and IgG2b deletion mutants at positions 233-235 of 34-3C anti-RBC Abs were generated, and their ability to initiate effector functions and their pathogenicity were compared with those of the respective wild-type Abs. The insertion of amino acid residues at positions 233-235 enabled the IgG1 subclass to bind FcgammaRIV but did not improve the binding to C1q. Accordingly, its pathogenicity was enhanced but still inferior to that of IgG2b. In contrast, the IgG2b deletion mutant lost its ability to bind to FcgammaRIV and activate complement. Consequently, its pathogenicity was markedly diminished to a level comparable to that of IgG1. Our results demonstrated that the initiation of FcgammaR- and complement-mediated effector functions of IgG2b was profoundly affected by the three amino acid deletion at positions 233-235, but that this natural three amino acid deletion could only partially explain the poor binding of IgG1 to FcgammaRIV and C1q. This indicates the lack in the IgG1 subclass of as yet unknown motifs promoting efficient interaction with FcgammaRIV and C1q. 相似文献
69.
Reverse structure of carnosine-induced sedative and hypnotic effects in the chick under acute stress
Tsuneyoshi Y Yamane H Tomonaga S Morishita K Denbow DM Furuse M 《Life sciences》2008,82(21-22):1065-1069
In the central nervous system, beta-alanine is thought to act as an inhibitory neurotransmitter, but the role or precise mechanism of beta-alanine in the brain has not been clearly defined. beta-Alanine is found in high levels in the chicken brain as a component of the dipeptides carnosine (beta-alanyl-L-histidine) and anserine, or as a free amino acid. We focused on the position of beta-alanine, i.e., at the carboxyl terminus. In Experiment 1, the central effects of glycyl-beta-alanine, L-histidyl-beta-alanine and L-valyl-beta-alanine were compared with a saline control in chicks. L-Histidyl-beta-alanine significantly induced sedative and hypnotic effects. In Experiment 2, the effects of carnosine, its reverse (L-histidyl-beta-alanine), and their combination were investigated. Central carnosine-induced hyperactivity while reverse carnosine-induced hypoactivity, and the behaviors were intermediate following the combination of the two peptides. Finally, the central effect of reverse carnosine was compared with beta-alanine alone and L-seryl-beta-alanine in Experiment 3. Reverse carnosine showed similar effects to beta-alanine. In conclusion, L-histidyl-beta-alanine not only has the reverse structure of carnosine, but also reverse function. Thus, we propose to name reverse carnosine (L-histidyl-beta-alanine) rev-carnosine. 相似文献
70.
Genomic and genetic analysis of Myb-related genes that regulate anthocyanin biosynthesis in grape berry skin 总被引:2,自引:0,他引:2