全文获取类型
收费全文 | 871篇 |
免费 | 64篇 |
出版年
2022年 | 2篇 |
2021年 | 7篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 7篇 |
2017年 | 10篇 |
2016年 | 17篇 |
2015年 | 15篇 |
2014年 | 29篇 |
2013年 | 48篇 |
2012年 | 48篇 |
2011年 | 64篇 |
2010年 | 37篇 |
2009年 | 33篇 |
2008年 | 41篇 |
2007年 | 64篇 |
2006年 | 70篇 |
2005年 | 62篇 |
2004年 | 57篇 |
2003年 | 59篇 |
2002年 | 38篇 |
2001年 | 13篇 |
2000年 | 12篇 |
1999年 | 17篇 |
1998年 | 14篇 |
1997年 | 9篇 |
1996年 | 12篇 |
1995年 | 6篇 |
1994年 | 8篇 |
1993年 | 6篇 |
1992年 | 20篇 |
1991年 | 21篇 |
1990年 | 13篇 |
1989年 | 12篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1965年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有935条查询结果,搜索用时 31 毫秒
61.
62.
Adoptive immunotherapy of cancer using activated Autologous lymphocytes-current status and new strategies- 总被引:14,自引:0,他引:14
Yamaguchi Y Ohshita A Kawabuchi Y Ohta K Shimizu K Minami K Hihara J Miyahara E Toge T 《Human cell》2003,16(4):183-189
After the discovery of interleukin-2 (IL-2), lymphokine-activated killer (LAK) cells, tumor-infiltrating lymphocytes (TILs), and cytotoxic T lymphocytes (CTLs) sensitized with the mixed lymphocyte-tumor culture (MLTC) system have been conducted in adoptive immunotherapy (AIT) trials during past 15 years. Although the overall response rate of tumor shrinkage was marginal (9%), locoregional administration of TILs for malignant effusions was effective (77%) for a decrease or disappearance of the effusions even in terminally-ill patients, resulting in an improvement of QOL. Recent advances for molecular understanding of antigen presentation and recognition have promoted us to enhance the efficacy of AIT by using cultured dendritic cells (DCs) for generating antigen-specific CTLs in vitro. The peptide-pulsed DC-activated killer (PDAK) cells showed tumor recognition against antigen-expressing cells, and were efficiently propagated with the IL2 plus immobilized anti-CD3 antibody (IL-2/CD3) culture system. Clinical trials using PDAK cells against patients with lung metastases are now progressed, in which peptides suitable for generating CTLs were chosen in individual patients using the method designated as host-oriented peptide evaluation (HPOE) approach. Moreover, DCs were introduced with tumor-derived RNA, which was amplified with the T7 promoter system, and then were used for stimulating lymphocytes. The tumor RNA-introduced DC-activated killer (TRiDAK) cells showed tumor-specific interferon-gamma spots even in a patient in whom we failed to generate PDAK cells using DCs and peptides, suggesting that the clinical trial of AIT using TRiDAK cells is warranted for the treatment of patients with metastatic cancer. Thus, more understanding of antigen-presentation and -recognition mechanisms and immune regulation systems may promote clinical applications of AIT to establish a novel modality of cancer treatment. 相似文献
63.
Mikata Y Takagi S Tanahashi M Ishii S Obata M Miyamoto Y Wakita K Nishisaka T Hirano T Ito T Hoshino M Ohtsuki C Tanihara M Yano S 《Bioorganic & medicinal chemistry letters》2003,13(19):3289-3292
Sugar-pendant [60] fullerene derivatives have been prepared from carbohydrate-linked azides 1a-e. Both monosugar (4a-e) and bissugar derivatives (5a-e) produce singlet oxygen ((1)O(2)) under laser irradiation (355 nm) proved by the direct observation of (1)O(2) emission at 1270 nm. Monosugar derivatives exhibit photocytotoxicity varying by the attached sugar molecule. 相似文献
64.
A two-hit model for development of multiple endocrine neoplasia type 2B by RET mutations 总被引:2,自引:0,他引:2
Iwashita T Murakami H Kurokawa K Kawai K Miyauchi A Futami H Qiao S Ichihara M Takahashi M 《Biochemical and biophysical research communications》2000,268(3):804-808
Multiple endocrine neoplasia (MEN) type 2B mutations have been reported at methionine 918 or alanine 883 in the tyrosine kinase domain of the RET proto-oncogene. Recently, a new combination of two germline missense mutations at valine 804 and tyrosine 806 was identified in a patient with MEN 2B-like clinical phenotypes including medullary thyroid carcinoma, mucosal neuroma, and marfanoid habitus. In this case, valine 804 and tyrosine 806 were replaced with methionine and cysteine, respectively. In the present study, biological activities of RET with these new mutations were compared with those with known MEN 2A or MEN 2B mutations. The transforming activity of RET with the V804M/Y806C mutation was about 8- to 13-fold higher than that of RET with a single V804M or Y806C mutation. Like RET with the M918T or A883F MEN 2B mutation, the transforming activity of RET with the V804M/Y806C mutation was not affected by substitution of phenylalanine for tyrosine 905 that abolished the activity of RET with the MEN 2A mutation. On the other hand, substitution of phenylalanine for tyrosines 864 and 952 drastically diminished the activity of RET with the V804M/Y806C, M918T or A883F mutation, suggesting that these three mutant proteins have similar biological properties. 相似文献
65.
Asano N Nishida M Miyauchi M Ikeda K Yamamoto M Kizu H Kameda Y Watson AA Nash RJ Fleet GW 《Phytochemistry》2000,53(3):379-382
Adenophora triphylla var. japonica (Campanulaceae) yielded two new alkaloids, the 6-C-butyl derivative of 2R,5R-bis(hydroxymethyl)-3R,4R-dihydroxypyrrolidine (DMDP) and alpha-1-C-ethyl-fagomine, together with the known alkaloids 1,4-dideoxy-1,4-imino-D-arabinitol, 1-deoxynojirimycin, and 1-deoxymannojirimycin. 6-C-Butyl-DMDP showed inhibitory activity toward almond beta-glucosidase (IC50 = 68 microM), whereas alpha-1-C-ethyl-fagomine inhibited bovine liver beta-galactosidase (IC50 = 29 microM). 相似文献
66.
A Miyauchi S Ebisu K Uchida M Yoshida M Ozawa T Tojo K Kadowaki H Takagi 《Journal of industrial microbiology & biotechnology》1998,21(4-5):208-214
Recombinant Bacillus brevis which carried an expression plasmid encoding the human epidermal growth factor (EGF) gene on a cryptic high-copy number plasmid,
pHT926, extracellularly produced EGF in its biologically active form at a concentration of over 1.5 g L−1 in the culture broth in a 30-L jar fermenter. The culture broth also contained some other EGF compounds, which mainly consisted
of oligomeric and polymeric forms with disulfide bonds. We developed a simple purification method for EGF, without prior cell
removal from the culture broth, comprising cation exchange expanded bed adsorption followed by ultrafiltration with UF 10 000
and 3000 membranes. The EGF compounds were efficiently separated from the EGF in its native form in the expanded bed adsorption
step. With this purification method, only EGF in its native form was recovered from the culture broth, with a yield of nearly
80%, and 90% purity. This efficient and economic system has made it possible to use EGF as a pharmaceutical in the livestock
industry.
Received 10 June 1998/ Accepted in revised form 10 September 1998 相似文献
67.
Exercise causes tissue-specific enhancement of endothelin-1 mRNA expression in internal organs 总被引:1,自引:0,他引:1
Maeda Seiji; Miyauchi Takashi; Kobayashi Tsutomu; Goto Katsutoshi; Matsuda Mitsuo 《Journal of applied physiology》1998,85(2):425-431
Endothelin-1 (ET-1) is a potent vasoconstrictorpeptide, which also potentiates contractions to norepinephrine in humaninternal mammary and coronary vessels. Exercise causes a redistribution of blood flow, i.e., the increase in working muscles that is partly attributable to a decrease in visceral blood flow. We hypothesized thatexercise causes a tissue-specific increase in ET-1 expression ininternal organs. We studied whether exercise affects expression ofpreproET-1 mRNA in the kidneys and lungs. The rats performed treadmillrunning (0% grade) for 45 min at a speed of 25 m/min. The plasmaconcentrations of ET-1, epinephrine, and norepinephrine were greater inthe exercise rats than in the sedentary control rats. The expression ofpreproET-1 mRNA in the kidneys was markedly higher in the exercise ratsthan in the sedentary control rats, whereas that in the lungs did notdiffer between the two groups. Therefore, the present study provides apossibility that the exercise-induced increase in production of ET-1 inthe kidneys causes vasoconstriction and hence decreases blood flow inthe kidneys through its direct vasoconstrictive action and/orits indirect effect of enhancing vasoconstrictions to norepinephrine. 相似文献
68.
Ryosuke Tateishi Nobuko Akiyama Maki Miyauchi Riko Yoshinaga Hiroki Sasanuma Takashi Kudo Miki Shimbo Masahiro Shinohara Koji Obata Jun-ichiro Inoue Masaki Shirakawa Dai Shiba Hiroshi Asahara Nobuaki Yoshida Satoru Takahashi Hironobu Morita Taishin Akiyama 《PloS one》2015,10(10)
Gravity change affects many immunological systems. We investigated the effects of hypergravity (2G) on murine thymic cells. Exposure of mice to 2G for three days reduced the frequency of CD4+CD8+ thymocytes (DP) and mature medullary thymic epithelial cells (mTECs), accompanied by an increment of keratin-5 and keratin-8 double-positive (K5+K8+) TECs that reportedly contain TEC progenitors. Whereas the reduction of DP was recovered by a 14-day exposure to 2G, the reduction of mature mTECs and the increment of K5+K8+ TEC persisted. Interestingly, a surgical lesion of the inner ear’s vestibular apparatus inhibited these hypergravity effects. Quantitative PCR analysis revealed that the gene expression of Aire and RANK that are critical for mTEC function and development were up-regulated by the 3-day exposure and subsequently down-regulated by the 14-day exposure to 2G. Unexpectedly, this dynamic change in mTEC gene expression was independent of the vestibular apparatus. Overall, data suggest that 2G causes a temporary reduction of DP and a persistent reduction of mature mTECs in a vestibular system-dependent manner, and also dysregulates mTEC gene expression without involving the vestibular system. These data might provide insight on the impact of gravity change on thymic functions during spaceflight and living. 相似文献
69.
Daniele Magistro Hikaru Takeuchi Keyvan Kashkouli Nejad Yasuyuki Taki Atsushi Sekiguchi Rui Nouchi Yuka Kotozaki Seishu Nakagawa Carlos Makoto Miyauchi Kunio Iizuka Ryoichi Yokoyama Takamitsu Shinada Yuki Yamamoto Sugiko Hanawa Tsuyoshi Araki Hiroshi Hashizume Yuko Sassa Ryuta Kawashima 《PloS one》2015,10(9)
Processing speed is considered a key cognitive resource and it has a crucial role in all types of cognitive performance. Some researchers have hypothesised the importance of white matter integrity in the brain for processing speed; however, the relationship at the whole-brain level between white matter volume (WMV) and processing speed relevant to the modality or problem used in the task has never been clearly evaluated in healthy people. In this study, we used various tests of processing speed and Voxel-Based Morphometry (VBM) analyses, it is involves a voxel-wise comparison of the local volume of gray and white, to assess the relationship between processing speed and regional WMV (rWMV). We examined the association between processing speed and WMV in 887 healthy young adults (504 men and 383 women; mean age, 20.7 years, SD, 1.85). We performed three different multiple regression analyses: we evaluated rWMV associated with individual differences in the simple processing speed task, word–colour and colour–word tasks (processing speed tasks with words) and the simple arithmetic task, after adjusting for age and sex. The results showed a positive relationship at the whole-brain level between rWMV and processing speed performance. In contrast, the processing speed performance did not correlate with rWMV in any of the regions examined. Our results support the idea that WMV is associated globally with processing speed performance regardless of the type of processing speed task. 相似文献
70.
Yusuke Kawazoe Mutsumi Miyauchi Atsuhiro Nagasaki Hisako Furusho Syunryo Yanagisawa Chea Chanbora Toshihiro Inubushi Hideyuki Hyogo Takashi Nakamoto Keiko Suzuki Sawako Moriwaki Susumu Tazuma Shumpei Niida Takashi Takata 《PloS one》2015,10(9)