全文获取类型
收费全文 | 357篇 |
免费 | 13篇 |
国内免费 | 1篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 3篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 9篇 |
2014年 | 12篇 |
2013年 | 18篇 |
2012年 | 16篇 |
2011年 | 30篇 |
2010年 | 18篇 |
2009年 | 11篇 |
2008年 | 21篇 |
2007年 | 26篇 |
2006年 | 20篇 |
2005年 | 19篇 |
2004年 | 21篇 |
2003年 | 16篇 |
2002年 | 20篇 |
2001年 | 14篇 |
2000年 | 20篇 |
1999年 | 14篇 |
1998年 | 3篇 |
1997年 | 11篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1982年 | 2篇 |
排序方式: 共有371条查询结果,搜索用时 62 毫秒
61.
Tomohiro Yamaguchi Youichi Suzuki Ryuichi Katakura Takusaburo Ebina Junkichi Yokoyama Yoshiaki Fujimiya 《Cancer immunology, immunotherapy : CII》1998,47(2):97-103
γδT cells play a regulatory role in both primary and metastatic tumor growth in humans. The mechanisms responsible for the
activation and proliferation of circulating γδT cells should be fully understood prior to their adoptive transfer to cancer
patients. We have examined in vitro functional effects of interleukin-15 (IL-15) on highly purified γδT cells isolated from
glioblastoma patients. γδT cells constitutively express the heterotrimeric IL-2 receptor (IL-2R) αβγ, but the levels of IL-2Rβ
or γ expression were not increased by incubation with saturating amounts of IL-15. IL-15 was shown to induce a maximal γδT
cell proliferation, although at much higher concentrations (at least 2000 U/ml) than IL-2 (100 U/ml). Submaximal concentrations
of IL-15 plus low concentrations of IL-2 produced an additive proliferative response. In contrast to the IL-2-induced response,
this activity was completely or partially abrogated by anti-IL-2Rβ, or anti-IL-2Rγ antibodies, but not by anti-IL-2Rα antibodies.
Incubation of γδT cells in the presence of IL-15 resulted not only in the appearance of NK and LAK activity, but also in specific
autologous tumor cell killing activity, an additive effect being seen with IL-15 and IL-2. This IL-15-induced tumor-specific
activity could be significantly blocked by anti-IL-2Rγ and anti-IL-2R-β mAb, but not by anti-IL-2Rα mAb. Thus, in contrast
to IL-2, IL-15 activates tumor-specific γδT cells through the components of IL-2Rβ and IL-2Rγ, but not IL-2Rα. These enhanced
in vitro tumor-specific and proliferative responses of γδT cells seen with IL-15 suggest a rational adjuvant imunotherapeutic
use of γδT cells in cancer patients.
Received: 23 January 1998 / Accepted: 20 May 1998 相似文献
62.
Yoshiaki Fujimiya Youichi Suzuki Ko-ichi Oshiman Hidekazu Kobori Koichi Moriguchi Hisako Nakashima Yonezo Matumoto Shogo Takahara Takusaburo Ebina Ryuichi Katakura 《Cancer immunology, immunotherapy : CII》1998,46(3):147-159
We have isolated a novel type of natural tumoricidal product from the basidiomycete strain, Agaricus blazei Murill. Using the double-grafted tumor system in Balb/c mice, treatment of the primary tumor with an acid-treated fraction
(ATF) obtained from the fruit bodies resulted in infiltration of the distant tumor by natural killer (NK) cells with marked
tumoricidal activity. As shown by electrophoresis and DNA fragmentation assay, the ATF also directly inhibited tumor cell
growth in vitro by inducing apoptotic processing; this apoptotic effect was also demonstrated by increased expression of the
Apo2.7 antigen on the mitochondrial membranes of tumor cells, as shown by flow-cytometric analysis. The ATF had no effect
on normal mouse splenic or interleukin-2-treated splenic mononuclear cells, indicating that it is selectively cytotoxic for
the tumor cells. Cell-cycle analysis demonstrated that ATF induced the loss of S phase in MethA tumor cells, but did not affect
normal splenic mononuclear cells, which were mainly in the G0G1 phase. Various chromatofocussing purification steps and NMR
analysis showed the tumoricidal activity to be chiefly present in fractions containing (1→4)-α-D-glucan and (1→6)-β-D-glucan, present in a ratio of approximately 1:2 in the ATF (molecular mass 170 kDa), while the final purified fraction, HM3-G
(molecular mass 380 kDa), with the highest tumoricidal activity, consisted of more than 90% glucose, the main component being
(1→4)-α-D-glucan with (1→6)-β branching, in the ratio of approximately 4:1.
Received: 27 August 1997 / Accepted 22 December 1997 相似文献
63.
64.
FGF-2 suppresses cellular senescence of human mesenchymal stem cells by down-regulation of TGF-beta2 总被引:2,自引:0,他引:2
Ito T Sawada R Fujiwara Y Seyama Y Tsuchiya T 《Biochemical and biophysical research communications》2007,359(1):108-114
Human mesenchymal stem cells (hMSCs) are able to both self-replicate and differentiate into a variety of cell types. Fibroblast growth factor-2 (FGF-2) stimulates the growth of hMSCs in vitro, but its mechanisms have not been clarified yet. In this study, we investigated whether cellular senescence was involved in the stimulation of hMSCs growth by FGF-2 and the expression levels of transforming growth factor-beta1 and -beta2 (TGF-betas). Because hMSCs were induced cellular senescence due to long-term culture, FGF-2 decreased the percentage of senescent cells and suppressed G1 cell growth arrest through the suppression of p21(Cip1), p53, and p16(INK4a) mRNA expression levels. Furthermore, the levels of TGF-betas mRNA expression in hMSCs were increased by long-term culture, but FGF-2 suppressed the increase of TGF-beta2 mRNA expression due to long-term culture. These results suggest that FGF-2 suppresses the hMSCs cellular senescence dependent on the length of culture through down-regulation of TGF-beta2 expression. 相似文献
65.
We have succeeded in establishing a method to reproducibly immortalize human T cells by oncogene(s) transfection (Alam, 1997).
This study was based on our previous discoveries that these immortalized T cell lines contained T cells which showed cytotoxicity
against K562 cells in MHC-nonrestricted manner. Then we attempted to obtain human T cell clones exhibiting natural killer-like
activity. Here, we tried to establish clones from these immortalized T cell lines by limiting dilution after stimulation with
K562 cells, and then obtained 16 T cell clones. Two clones among them maintained their stability and showed vigorous growth
phenotype. Thus we selected these two clones for further analysis. One is derived from the T cell line transfected with oncogenes
ras and fos, the other is from the T cell line transfected with myc and fos. Both clones were demonstrated to be CD4+ T cells, indicating that CD4+ T cells were preferably expanded from T cell lines immortalized by oncogene transfection. These two clones showed cytotoxicity
against K562 cells, indicating that these two T cell clones still retain a natural killer-like activity of killing target
cells of K562 cells in a MHC-nonrestricted manner. The natural killer-like activity of the T cell clones was shown to be stable
for more than 2 yr when cultured in the presence of IL-2, indicating that introduction of two oncogenes such as ras/fos or
myc/fos resulted in the acquisition of infinite replicative life-span but not in transformational alteration of cellular function.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
66.
67.
Kiichiro Teruya Yoshihito Daimon Xiao-Yan Dong Yoshinori Katakura Takumi Miura Akira Ichikawa Tsukasa Fujiki Makiko Yamashita Tetsuya Mori Hideya Ohashi Sanetaka Shirahata 《Cytotechnology》2005,47(1-3):29-36
The cell line D29, which was easily and rapidly established by the promoter-activated production and glutamine synthetase
hybrid system, secreted recombinant human interleukin-6 (hIL-6) at a productivity rate of 39.5 μg 10−6 cells day−1, one of the highest reported levels worldwide. The productivity rate was about 130-fold higher than that of the cell line
A7, which was established without both promoter activation and gene amplification. Although D29 cells had a high copy number
and high mRNA level of the hIL-6 gene as well as a high secretion rate of hIL-6, large amounts of intracellular hIL-6 protein
accumulated in D29 cells compared to A7 cells. Northern blotting analysis showed no change in the GRP78/BiP expression level
in D29 cells. In contrast, an electrophoresis mobility shift assay revealed strong activation of NF-κB in D29 cells. These
results suggest that large amounts of hIL-6 translated from large amounts of hIL-6 mRNA cause excess accumulation of intact
hIL-6 in the endoplasmic reticulum (ER), and that subsequent negative feedback signals via the ER overload response inhibit
hIL-6 protein secretion. To enhance the hIL-6 productivity rate of D29 cells by releasing the negative feedback signals, the
effect of pyrrolidinedithiocarbamate, an inhibitor of NF-κB activation, was examined. Suppression of NF-κB activation in D29
cells produced a 25% augmentation of the hIL-6 productivity rate. Therefore, in highly productive cells like D29 cells, the
release of negative feedback signals could increase the total amount of recombinant protein secretion. 相似文献
68.
CONTRIBUTION OF MULTIPLE ISOLATING BARRIERS TO REPRODUCTIVE ISOLATION BETWEEN A PAIR OF PHYTOPHAGOUS LADYBIRD BEETLES 总被引:1,自引:0,他引:1
Kei W. Matsubayashi Haruo Katakura 《Evolution; international journal of organic evolution》2009,63(10):2563-2580
Reproductive isolation between species may often be attained by multiple isolating barriers, but the components are rarely studied in animal taxa. To elucidate the nature of multiple isolating barriers, we quantified the strength of three premating barriers, including ecologically based ones (seasonal, habitat, and sexual), two postmating–prehatching barriers (reduced egg hatchability and conspecific sperm precedence [CSP]), and one posthatching barrier, including four components of F1 hybrid reduced fitness, between two phytophagous ladybird beetles, Henosepilachna vigintioctomaculata and H. pustulosa . We detected five positive barriers (habitat isolation, sexual isolation, reduced egg hatchability, CSP, and reduced egg hatchability in backcrosses of F1 hybrids). None of these barriers entirely prevents gene exchange when it acts alone, but jointly they generate nearly complete reproductive isolation even between sympatric populations. Host fidelity contributed most strongly to reproductive isolation by reducing interspecific hybridization through several important types of ecological isolation, including microspatial, habitat, and seasonal isolation. The existence of multiple isolating barriers likely helps keep reproductive isolation stable and robust, by complementing changes in the strength of leaky barriers. This complementarity of multiple isolating barriers yields the concept of robustness of reproductive isolation, which is important when considering the long-term maintenance of species boundaries in coexisting species pairs. 相似文献
69.
Michio Hashimoto Hossain Md Shahdat Masanori Katakura Yoko Tanabe Shuji Gamoh Koji Miwa Toshio Shimada Osamu Shido 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2009,1791(4):289-296
Amyloid β peptide25–35 (Aβ25–35) encompasses one of the neurotoxic domains of full length Aβ1–40/42, the major proteinaceous component of amyloid deposits in Alzheimer's disease (AD). We investigated the effect of docosahexaenoic acid (DHA, 22:6, n-3), an essential brain polyunsaturated fatty acid, on the in vitro fibrillation of Aβ25–35 and found that it significantly reduced the degree of fibrillation, as shown by a decrease in the intensity of both the thioflavin T and green fluorescence in confocal microscopy. Transmission electron microscopy revealed that DHA-incubated samples were virtually devoid of structured fibrils but had an amorphous-like consistency, whereas the controls contained structured fibers of various widths and lengths. The in vitro fibrillation of Aβ25–35 appeared to be pH-dependent, with the strongest effect seen at pH 5.0. DHA inhibited fibrillation at all pHs, with the strongest effect at pH 7.4. It also significantly decreased the levels of Aβ25–35 oligomers. Nonreductive gradient gel electrophoresis revealed that the molecular size of the oligomers of Aβ25–35 was 10 kDa (equivalent to decamers of Aβ25–35) and that DHA dose-dependently reduced these decamers. These results suggest that DHA decreases the in vitro fibrillation of Aβ25–35 by inhibiting the oligomeric amyloid species and, therefore, Aβ25–35-related neurotoxicity or behavioral impairment could be restrained by DHA. 相似文献
70.
Tetherin (also known as BST2, CD317 or HM1.24) has recently been reported to inhibit a wide range of viruses. However, the antiviral mechanism of action of tetherin has not been determined. Both ends of the tetherin molecule are associated with the plasma membrane and it forms a homodimer. Therefore, a model in which progeny virions are retained on the cell surface by dimer formation between tetherin molecules on the viral envelope and plasma membrane has been proposed as the antiviral mechanism of action of this molecule. To investigate this possibility, we examined the correlation between dimerization and antiviral activity of tetherin in Lassa and Marburg virus-like particle production systems using tetherin mutants deficient in dimer formation. However, the tetherin mutant with complete loss of dimerization activity still showed apparent antiviral activity, indicating that dimerization of tetherin is not essential for its antiviral activity. This suggests that tetherin retains progeny virions on the cell surface by a mechanism other than dimerization. 相似文献