全文获取类型
收费全文 | 828篇 |
免费 | 44篇 |
专业分类
872篇 |
出版年
2022年 | 2篇 |
2021年 | 4篇 |
2019年 | 3篇 |
2018年 | 7篇 |
2017年 | 7篇 |
2016年 | 9篇 |
2015年 | 18篇 |
2014年 | 17篇 |
2013年 | 35篇 |
2012年 | 40篇 |
2011年 | 55篇 |
2010年 | 16篇 |
2009年 | 23篇 |
2008年 | 36篇 |
2007年 | 47篇 |
2006年 | 32篇 |
2005年 | 33篇 |
2004年 | 39篇 |
2003年 | 38篇 |
2002年 | 32篇 |
2001年 | 40篇 |
2000年 | 38篇 |
1999年 | 30篇 |
1998年 | 13篇 |
1997年 | 10篇 |
1996年 | 16篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1993年 | 11篇 |
1992年 | 30篇 |
1991年 | 22篇 |
1990年 | 26篇 |
1989年 | 15篇 |
1988年 | 15篇 |
1987年 | 12篇 |
1986年 | 20篇 |
1985年 | 15篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
排序方式: 共有872条查询结果,搜索用时 0 毫秒
821.
Direct interaction between a quinoline derivative, MS-209, and multidrug resistance protein (MRP) in human gastric cancer cells 总被引:4,自引:0,他引:4
Nakamura T Oka M Aizawa K Soda H Fukuda M Terashi K Ikeda K Mizuta Y Noguchi Y Kimura Y Tsuruo T Kohno S 《Biochemical and biophysical research communications》1999,255(3):618-624
MS-209 is a novel quinoline derivative reversing P-glycoprotein-mediated multidrug resistance (MDR). We investigated the interaction between MS-209 and multidrug resistance protein (MRP) in MRP-overexpressing human gastric cancer cells. We measured [3H]leukotriene C4 uptake into the membrane vesicles of the cells and intracellular calcein and [3H]vincristine accumulation with or without MS-209. In multi-drug-resistant MKN45R0.8 cells selected by doxorubicin, MS-209 dose dependently reduced MRP-mediated [3H]leukotriene C4 uptake and increased calcein accumulation. In both resistant and unselected cell lines expressing the MRP gene, MS-209 increased [3H]vincristine accumulation in proportion with the level of MRP mRNA expression and enhanced the cytotoxicity of etoposide, doxorubicin, and vincristine. The reversal effects correlated with the level of MRP mRNA expression in these cells. Our results indicate that MS-209 effectively reverses intrinsic and acquired MRP-mediated MDR of gastric cancer cells by interacting directly with MRP. 相似文献
822.
To ascertain the feeding habits of benthic juvenile yellowfin goby Acanthogobius flavimanus, the gut contents of 599 specimens (15–41 mm in standard length, SL), collected on a tidal mudflat in the Tama River estuary
throughout the diel cycle, were examined. The major prey items changed from harpacticoid copepods to errant and sedentary
polychaetes at ca. 20 mm SL. Prey width increased with fish size. Fish of 26–28 mm SL fed mainly from sunset to morning, with
highest feeding intensity during twilight hours and/or high tide. Based on the gut evacuation rate estimated from a forced
feeding experiment in the laboratory and data for the diel change of mean gut-content volume in the field, the daily ration
of juvenile yellowfin goby (26–28 mm SL) was calculated to be 13.8 mm3 fish−1 day−1. This volume is approximately equivalent to 3.9 individuals of the errant polychaete Ceratonereis erythraeensis (9.7 mm in body length, BL) or 8.1 individuals of the sedentary polychaete Prionospio japonica (14.8 mm BL), both species occurring abundantly on the mudflat during the study. 相似文献
823.
Yoshitomo Morinaga Katsunori Yanagihara Shigeki Nakamura Hiroo Hasegawa Masafumi Seki Koichi Izumikawa Hiroshi Kakeya Yoshihiro Yamamoto Yasuaki Yamada Shigeru Kohno Shimeru Kamihira 《Respiratory research》2010,11(1):158
Background
Legionella pneumophila (LPN) can cause a lethal infectious disease with a marked inflammatory response in humans. However, the mechanism of this severe inflammation remains poorly understood. Since necrosis is known to induce inflammation, we investigated whether LPN induces necrosis in macrophages. We also analyzed the involvement of lysosomal cathepsin B in LPN-induced cell death.Methods
The human monocytic cell line THP-1 was infected with LPN, NUL1 strain. MG132-treated cells were used as apoptotic control cells. After infection, the type of cell death was analyzed by using microscopy, LDH release and flow cytometry. As a proinflammatory mediator, high-mobility group box 1 (HMGB-1), was measured. Cathepsin B activity was also measured and the inhibitory effects of cathepsin B on LPN-induced cell death were analyzed.Results
THP-1 cells after treatment with high dose of LPN showed necrotic features with releasing HMGB-1. This necrosis and the HMGB-1 release were inhibited by a specific lysosomal cathepsin B inhibitor and were characterized by a rapid and high activation of cathepsin B that was not observed in apoptotic control cells. The necrosis was also accompanied by cathepsin B-dependent poly(ADP-ribose) polymerase (PARP) cleavage.Conclusions
We demonstrate here that L. pneumophila rapidly induces cathepsin B-dependent necrosis in a dose-dependent manner and releases a proinflammatory mediator, HMGB-1, from macrophages. This report describes a novel aspect of the pathogenesis of Legionnaires'' disease and provides a possible therapeutic target for the regulation of inflammation. 相似文献824.
Postnatal Development of Noradrenaline and 3-Methoxy-4-Hydroxyphenylethyleneglycol Sulphate Levels in Rat Brain Regions 总被引:1,自引:2,他引:1
Yasuko Kohno Masatoshi Tanaka Ryoichi Nakagawa Yoshishige Ida Kenichiro Iimori Nobuyuki Nagasaki 《Journal of neurochemistry》1982,39(3):878-881
Abstract: Developmental changes in brain levels of noradrenaline (NA) and 3-methoxy-4-hydroxyphenylethyleneglycolsulphate (MHPG-SO4 ) were studied in rats. In most brain regions, MHPG-SO4 level rapidly increased to approach or exceed adult levels at the time of weaning, while NA levels increased more gradually and reached adult levels following weaning, Pharmacological studies showed that the MHPG-SO4 level in the neonatal brain reflects the degradation of released NA. The developmental characteristics of noradrenergic neurons in eight discrete brain regions are discussed. 相似文献
825.
Makoto Watanabe Masahiro Yamaguchi Chikako Tabe Mayumi Iwasaki Rie Yamashita Ryo Funada Motohiro Fukami Hideyuki Matsumura Yoshihisa Kohno Takeshi Izuta 《Trees - Structure and Function》2007,21(4):421-432
The objectives of this study were to clarify the influences of nitrogen (N) load on the growth and photosynthetic responses
of Quercus serrata seedlings to O3 and to obtain basic data for evaluating the critical levels of O3 for protecting Q. serrata forests in Japan. The effects of O3 and/or N load on growth and photosynthetic activity of Q. serrata seedlings were investigated during the two growing seasons. Two-year-old seedlings were assigned to 12 experimental treatments,
which were comprised of the combination of four gas treatments (charcoal-filtered air and three levels of O3 at 1.0, 1.5 and 2.0 times ambient concentration) and three N treatments (0, 20 and 50 kg ha−1 year−1). During the second growing season, no significant interactive effects of O3 and N load on the growth and net photosynthetic rate of the seedlings were detected. Threrfore, we concluded that N supply
to the soil at ≤50 kg ha−1 year−1 does not significantly influence the growth and photosynthetic responses of Q. serrata seedlings to O3. Based on the O3 exposure-response relationships for the whole-plant growth of the seedlings, the critical level of O3 for Q. serrata was estimated to be approximately 36 nmol mol−1 as the average 15-h O3 concentration during the one growing season. 相似文献
826.
827.
M. J. Micallef Kenshi Yoshida Sachiko Kawai Toshiharu Hanaya Keizo Kohno Shigeyuki Arai Tadao Tanimoto Kakuji Torigoe Mitsukiyo Fujii Masao Ikeda Masashi Kurimoto 《Cancer immunology, immunotherapy : CII》1997,43(6):361-367
Interferon-γ-inducing factor/interleukin-18 is a novel cytokine that reportedly augments natural killer (NK) activity in
human and mouse peripheral blood mononuclear cell cultures in vitro and has recently been designated IL-18. In this study,
IL-18 exhibited significant antitumor effects in BALB/c mice challenged intraperitoneally (i.p.) with syngeneic Meth A sarcoma
when administered i.p. on days 1, 2 and 3 after challenge. Intravenous (i.v.) administration also induced antitumor effects
in the tumor-bearing mice; however, subcutaneous (s.c.) administration did not. When mice were twice pretreated with 1 μg
IL-18 3 days and 6 h before tumor challenge, all mice survived whereas control mice died within 3 weeks of challenge. Inhibitory
effects on Meth A cell growth in vitro were not observed with either IL-18 or interferon γ. The effects of IL-18 pretreatment
were abrogated by abolition of NK activity after mice had been injected with anti-asialo GM1 antibody 48 h before and, 24
h and 72 h after tumor challenge. Mice pretreated with IL-18 and surviving tumor challenge resisted rechallenge with Meth
A cells but could not reject Ehrlich ascites carcinoma, and spleen cells from the resistant mice, but not control mice, exhibited
cytotoxic activity against Meth A cells in vitro after restimulation with mitomycin C-treated Meth A cells for 5 days. The
effector cells in the spleen cell preparations from resistant mice appear to be CD4+ cells because cytolytic activity was significantly inhibited after depletion of this subset by monoclonal antibodies and
complement. In conclusion, IL-18 exhibits in vivo immunologically (primarily NK) mediated antitumor effects in mice challenged
with syngeneic Meth A sarcoma and induces immunological memory and the generation of cytotoxic CD4+ cells.
Received: 17 September 1996 / Accepted: 8 November 1996 相似文献
828.
Cytogenetic studies were performed on two types of Japanese hagfish (Eptatretus okinoseanus) that eliminate about 45% (type A) and 55% (type B) of their DNA from presumptive somatic cells during the differentiation of somatic cells. The observations revealed inter- and intraindividual variations in the number of chromosomes in germ cells of both types of hagfishes. Although the modal number of chromosomes in the germ cells was 54 in both types, the percentage of cells with the modal number was rather low (38.6% [51/132] in five specimens of type A and 22.7% [25/110] in eight specimens of type B). In addition, one of seven type B specimens clearly had a modal number of 62 chromosomes. Another specimen of type B had a bimodal distribution of chromosome numbers, with peaks of 54 and 59 chromosomes. The observation of interindividual variations was supported by data on the amount of DNA in germ cells of type B specimens. However, these variations were rarely observed in somatic cells. These results suggest that supernumerary (B) chromosomes are maintained in germ cells and are eliminated together with some other chromosomes and/or chromatin from somatic cells. 相似文献
829.
Stability of YACs Containing Ribosomal or RCP/GCP Locus DNA in Wild-type S. cerevisiae and RAD Mutant Strains 总被引:1,自引:0,他引:1
Kohno Kyoko; Wada Morimasa; Schlessinger David; D'urso Michele; Tanabe Sumiko; Oshiro Tomoko; Imamoto Fumio 《DNA research》1994,1(4):191-199
About 2% of human YAC clones, including tandemly repeated segmentscolor vision pigment DNA, ribosomal DNA and alphoid DNA havebeen reported to be inherently unstable in yeast hosts, producingmore stable deletion products. YACs containing color visionred pigment gene DNA or 1.5 rDNA tandem repeat units were transformedinto hosts bearing lesions at the RAD1, RAD6, RAD51, or RAD52loci. YACs susceptible to deletion during outgrowth of wild-typecells (or in preliminary experiments, in RAD6 transformants)were stable for up to 100 generations or more in the other strains.Thus both the RAD1 and RAD51/RAD52 epistatic pathways are apparentlyinvolved in the instability of YACs containing tandem repeatloci, presumably during recombination-based deletion formation;and a yeast host disarmed in these pathways will likely maintainYACs intact that are otherwise unstable. 相似文献
830.
ABSTRACT: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma, which primarily occurs deep in the extremities, especially in skeletal muscle, or tendon. EMC of the pleura has been described, however, no case of primary EMC arising from lung has been previously reported. We describe herein, a 51-year-old Asian female initially manifested with signs of severe anemia who presented with a lung mass unrelated to pleura that was morphologically typical EMC, with strong immunoreactivity for vimentin and NSE. Two weeks after resection, the anemia was cured. The patient continued with follow-up, without sign of abnormality 32 months after operation.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2882199847396682. 相似文献