全文获取类型
收费全文 | 4079篇 |
免费 | 243篇 |
专业分类
4322篇 |
出版年
2022年 | 34篇 |
2021年 | 57篇 |
2020年 | 31篇 |
2019年 | 50篇 |
2018年 | 58篇 |
2017年 | 53篇 |
2016年 | 99篇 |
2015年 | 109篇 |
2014年 | 169篇 |
2013年 | 225篇 |
2012年 | 251篇 |
2011年 | 274篇 |
2010年 | 165篇 |
2009年 | 155篇 |
2008年 | 235篇 |
2007年 | 219篇 |
2006年 | 220篇 |
2005年 | 208篇 |
2004年 | 237篇 |
2003年 | 226篇 |
2002年 | 222篇 |
2001年 | 64篇 |
2000年 | 71篇 |
1999年 | 61篇 |
1998年 | 61篇 |
1997年 | 48篇 |
1996年 | 38篇 |
1995年 | 56篇 |
1994年 | 24篇 |
1993年 | 28篇 |
1992年 | 47篇 |
1991年 | 57篇 |
1990年 | 51篇 |
1989年 | 37篇 |
1988年 | 38篇 |
1987年 | 36篇 |
1986年 | 36篇 |
1985年 | 27篇 |
1984年 | 19篇 |
1983年 | 28篇 |
1982年 | 21篇 |
1980年 | 12篇 |
1979年 | 19篇 |
1978年 | 12篇 |
1977年 | 11篇 |
1974年 | 13篇 |
1972年 | 11篇 |
1970年 | 15篇 |
1969年 | 15篇 |
1967年 | 10篇 |
排序方式: 共有4322条查询结果,搜索用时 15 毫秒
61.
Naoshi Yamamoto Sayaka Ohrui Takahiro Okada Tsuyoshi Saitoh Noriki Kutsumura Yasuyuki Nagumo Yoko Irukayama-Tomobe Yasuhiro Ogawa Yukiko Ishikawa Yurie Watanabe Daichi Hayakawa Hiroaki Gouda Masashi Yanagisawa Hiroshi Nagase 《Bioorganic & medicinal chemistry》2019,27(8):1747-1758
Morphinan derivatives lacking the 4,5-epoxy ring were synthesized to examine the participation of the 14-OH group, the 3-OMe group, and the aromaticity of the A-ring in the activity and selectivity for the orexin 1 receptor (OX1R). The assay results and the conformational analyses of the 14-dehydrated and 14-H derivatives suggested that the orientations of the 6-amide side chain and the 17-benzenesulfonyl group would play important roles in the activity for OX1R. In the 6β-derivatives, removal of the 3-OMe group and the reduction of the A-ring significantly decreased the activity toward the OX1R, but these changes did not affect the 6α-derivatives. These results indicate that the 3-OMe group and the A-ring would be essential structural moieties for the 6β-derivatives. 相似文献
62.
63.
Satoh M Andoh Y Clingan CS Ogura H Fujii S Eshima K Nakayama T Taniguchi M Hirata N Ishimori N Tsutsui H Onoé K Iwabuchi K 《PloS one》2012,7(2):e30568
The progression of obesity is accompanied by a chronic inflammatory process that involves both innate and acquired immunity. Natural killer T (NKT) cells recognize lipid antigens and are also distributed in adipose tissue. To examine the involvement of NKT cells in the development of obesity, C57BL/6 mice (wild type; WT), and two NKT-cell-deficient strains, Jα18(-/-) mice that lack the type I subset and CD1d(-/-) mice that lack both the type I and II subsets, were fed a high fat diet (HFD). CD1d(-/-) mice gained the least body weight with the least weight in perigonadal and brown adipose tissue as well as in the liver, compared to WT or Jα18(-/-) mice fed an HFD. Histologically, CD1d(-/-) mice had significantly smaller adipocytes and developed significantly milder hepatosteatosis than WT or Jα18(-/-) mice. The number of NK1.1(+)TCRβ(+) cells in adipose tissue increased when WT mice were fed an HFD and were mostly invariant Vα14Jα18-negative. CD11b(+) macrophages (Mφ) were another major subset of cells in adipose tissue infiltrates, and they were divided into F4/80(high) and F4/80(low) cells. The F4/80(low)-Mφ subset in adipose tissue was increased in CD1d(-/-) mice, and this population likely played an anti-inflammatory role. Glucose intolerance and insulin resistance in CD1d(-/-) mice were not aggravated as in WT or Jα18(-/-) mice fed an HFD, likely due to a lower grade of inflammation and adiposity. Collectively, our findings provide evidence that type II NKT cells initiate inflammation in the liver and adipose tissue and exacerbate the course of obesity that leads to insulin resistance. 相似文献
64.
Hirai Nobuhiro; Kojima Yasuhiro; Koshimizu Koichi; Shinozaki Masateru; Takimoto Atsushi 《Plant & cell physiology》1993,34(7):1039-1044
Flowering of Pharbitis nil strain Violet is induced in continuouslight under poor nutritional conditions. High-performance liquidchromatography of extracts of the cotyledons revealed that twocompounds in addition to chlorogenic acid accumulate under suchconditions. The compounds were identified as pinoresinol glucosideand p-coumaroylquinic acid. The endogenous levels of these phenylpropanoidswere correlated with the flowering response when nutrition waspoor. However, activation of phenylpropanoid biosynthesis seemednot to be essential for the induction of flowering. (Received May 17, 1993; Accepted July 26, 1993) 相似文献
65.
66.
New and effective method for the Beckmann rearrangement of indanone oxime mesylate is described, in which a selective and controlled production of the isomeric isocarbostyrils is achieved. 相似文献
67.
Mark F. Santos Germana Rappa Jana Karbanov Cheryl Vanier Chikao Morimoto Denis Corbeil Aurelio Lorico 《Journal of cellular and molecular medicine》2019,23(6):4408-4421
The intercellular communication mediated by extracellular vesicles (EVs) has gained international interest during the last decade. Interfering with the mechanisms regulating this cellular process might find application particularly in oncology where cancer cell‐derived EVs play a role in tumour microenvironment transformation. Although several mechanisms were ascribed to explain the internalization of EVs, little is our knowledge about the fate of their cargos, which are crucial to mediate their function. We recently demonstrated a new intracellular pathway in which a fraction of endocytosed EV‐associated proteins is transported into the nucleoplasm of the host cell via a subpopulation of late endosomes penetrating into the nucleoplasmic reticulum. Silencing tetraspanin CD9 both in EVs and recipient cells strongly decreased the endocytosis of EVs and abolished the nuclear transfer of their cargos. Here, we investigated whether monovalent Fab fragments derived from 5H9 anti‐CD9 monoclonal antibody (referred hereafter as CD9 Fab) interfered with these cellular processes. To monitor the intracellular transport of proteins, we used fluorescent EVs containing CD9‐green fluorescent protein fusion protein and various melanoma cell lines and bone marrow‐derived mesenchymal stromal cells as recipient cells. Interestingly, CD9 Fab considerably reduced EV uptake and the nuclear transfer of their proteins in all examined cells. In contrast, the divalent CD9 antibody stimulated both events. By impeding intercellular communication in the tumour microenvironment, CD9 Fab‐mediated inhibition of EV uptake, combined with direct targeting of cancerous cells could lead to the development of novel anti‐melanoma therapeutic strategies. 相似文献
68.
Hirofumi Sakoguchi Tomoya Shintani Hironobu Ishiyama Ryo C. Yanagita Yasuhiro Kawanami 《Bioscience, biotechnology, and biochemistry》2013,77(12):2194-2197
ABSTRACTThe nematocidal activities of the fatty acid esters of d-allose were examined using the larvae of C. elegans. Among the fatty acid esters, 6-O-octanoyl-d-allose (3) showed significant activity. 6-O-octanoyl-d-glucose (5) showed no activity, indicating that the D-allose moiety is essential for the nematocidal activity of 3. A nonhydrolyzable alkoxy analog 6-O-octyl-d-allose (6) also showed activity equivalent to that of 3. 相似文献
69.
Masanori Asada Kazuhiro Morimoto Kazuhiro Nakanishi Ryuichi Matsuno Atsuo Tanaka Akira Kimura 《Bioscience, biotechnology, and biochemistry》2013,77(8):1773-1774
Arthrobacter simplex was screened as an α-keto-δ-guanidinovalerate (ketoarginine) assimilating organism. A characteristic feature was its growth on ketoarginine as a carbon source; it began to grow after an extremely long lag. Its growth was stimulated by addition of 0.02% yeast extract to the medium.The results indicated the transamination of arginine-α-ketoglutarate (α-KGA) and the hydrolyzing reaction of ketoarginine into α-keto-δ-aminovalerate and urea. Two intermediates, ketoarginine and α-keto-δ-aminovalerate, were isolated and identified by various procedures. Coupling of the two reactions was demonstrated in cell-free extracts of arginine-grown cells; ketoarginine formed from arginine by transamination with α-KGA was hydrolyzed directly to α-keto-δ-aminovalerate and urea. The metabolic routes of arginine in microorganisms were discussed. 相似文献
70.
Hiroyuki Morimoto Hirohiko Okamura Kaya Yoshida Seiichiro Kitamura Tatsuji Haneji 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):327-331
The reversible phosphorylation of proteins mediates cellular signals in eukaryotic cells. RNA interference inhibits the expression of genes and proteins in a sequence-specific manner and provides a tool to study the functions of target molecules. The effect of RNA interference on protein phosphatase isoforms in HEK-293 cells was examined. Protein phosphatase 1 delta (PP1δ) sequence-specific double-stranded RNA (dsRNA) inhibited mRNA and protein expression of the PP18. This RNA interference did not affect the expression of α and γ1 isoforms of PP1. Transfection of antisense RNA specific for PP1δ also suppressed the expression of PP1δ. It was further demonstrated by an in vitro RNA cleavage assay that extracts of HEK-293 cells catalyzed the processing of dsRNA. This cell line had much stronger mRNA expression of Dicer, an RNase III-like enzyme, than did human osteoblastic MG63 cells. The present results show that RNA interference is a useful tool to distinguish between PP1 isoforms. 相似文献