全文获取类型
收费全文 | 1142篇 |
免费 | 57篇 |
出版年
2023年 | 2篇 |
2022年 | 7篇 |
2021年 | 18篇 |
2020年 | 3篇 |
2019年 | 8篇 |
2018年 | 22篇 |
2017年 | 17篇 |
2016年 | 17篇 |
2015年 | 37篇 |
2014年 | 43篇 |
2013年 | 66篇 |
2012年 | 76篇 |
2011年 | 68篇 |
2010年 | 43篇 |
2009年 | 50篇 |
2008年 | 52篇 |
2007年 | 79篇 |
2006年 | 60篇 |
2005年 | 87篇 |
2004年 | 71篇 |
2003年 | 53篇 |
2002年 | 41篇 |
2001年 | 22篇 |
2000年 | 13篇 |
1999年 | 19篇 |
1998年 | 20篇 |
1997年 | 15篇 |
1996年 | 5篇 |
1995年 | 8篇 |
1994年 | 14篇 |
1993年 | 6篇 |
1992年 | 26篇 |
1991年 | 10篇 |
1990年 | 8篇 |
1989年 | 20篇 |
1988年 | 11篇 |
1987年 | 9篇 |
1986年 | 11篇 |
1985年 | 7篇 |
1984年 | 10篇 |
1983年 | 9篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1976年 | 6篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有1199条查询结果,搜索用时 15 毫秒
101.
Sato Tomonori Ito Yoshiaki Nagasawa Takashi 《Molecular and cellular biochemistry》2015,402(1-2):93-100
Molecular and Cellular Biochemistry - Muscle wasting impairs physical function and leads people to a bedridden state. We previously demonstrated that lysine (Lys) suppresses autophagic-proteolysis... 相似文献
102.
103.
Ann K. Rosenthal Claudia M. Gohr Elizabeth Mitton-Fitzgerald Rupinder Grewal James Ninomiya Carolyn B. Coyne William T. Jackson 《The Journal of biological chemistry》2015,290(21):13028-13038
Chondrocyte-derived extracellular organelles known as articular cartilage vesicles (ACVs) participate in non-classical protein secretion, intercellular communication, and pathologic calcification. Factors affecting ACV formation and release remain poorly characterized; although in some cell types, the generation of extracellular vesicles is associated with up-regulation of autophagy. We sought to determine the role of autophagy in ACV production by primary articular chondrocytes. Using an innovative dynamic model with a light scatter nanoparticle counting apparatus, we determined the effects of autophagy modulators on ACV number and content in conditioned medium from normal adult porcine and human osteoarthritic chondrocytes. Healthy articular chondrocytes release ACVs into conditioned medium and show significant levels of ongoing autophagy. Rapamycin, which promotes autophagy, increased ACV numbers in a dose- and time-dependent manner associated with increased levels of autophagy markers and autophagosome formation. These effects were suppressed by pharmacologic autophagy inhibitors and short interfering RNA for ATG5. Caspase-3 inhibition and a Rho/ROCK inhibitor prevented rapamycin-induced increases in ACV number. Osteoarthritic chondrocytes, which are deficient in autophagy, did not increase ACV number in response to rapamycin. SMER28, which induces autophagy via an mTOR-independent mechanism, also increased ACV number. ACVs induced under all conditions had similar ecto-enzyme specific activities and types of RNA, and all ACVs contained LC3, an autophagosome-resident protein. These findings identify autophagy as a critical participant in ACV formation, and augment our understanding of ACVs in cartilage disease and repair. 相似文献
104.
Akira Ishio Takeshi Sasamura Tomonori Ayukawa Junpei Kuroda Hiroyuki O. Ishikawa Naoki Aoyama Kenjiroo Matsumoto Takuma Gushiken Tetsuya Okajima Tomoko Yamakawa Kenji Matsuno 《The Journal of biological chemistry》2015,290(1):505-519
Notch (N) is a transmembrane receptor that mediates the cell-cell interactions necessary for many cell fate decisions. N has many epidermal growth factor-like repeats that are O-fucosylated by the protein O-fucosyltransferase 1 (O-Fut1), and the O-fut1 gene is essential for N signaling. However, the role of the monosaccharide O-fucose on N is unclear, because O-Fut1 also appears to have O-fucosyltransferase activity-independent functions, including as an N-specific chaperon. Such an enzymatic activity-independent function could account for the essential role of O-fut1 in N signaling. To evaluate the role of the monosaccharide O-fucose modification in N signaling, here we generated a knock-in mutant of O-fut1 (O-fut1R245A knock-in), which expresses a mutant protein that lacks O-fucosyltransferase activity but maintains the N-specific chaperon activity. Using O-fut1R245A knock-in and other gene mutations that abolish the O-fucosylation of N, we found that the monosaccharide O-fucose modification of N has a temperature-sensitive function that is essential for N signaling. The O-fucose monosaccharide and O-glucose glycan modification, catalyzed by Rumi, function redundantly in the activation of N signaling. We also showed that the redundant function of these two modifications is responsible for the presence of N at the cell surface. Our findings elucidate how different forms of glycosylation on a protein can influence the protein''s functions. 相似文献
105.
Physiological characterization of anaerobic ammonium oxidizing bacterium ‘Candidatus Jettenia caeni’
下载免费PDF全文
![点击此处可从《Environmental microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Muhammad Ali Mamoru Oshiki Takanori Awata Kazuo Isobe Zenichiro Kimura Hiroaki Yoshikawa Daisuke Hira Tomonori Kindaichi Hisashi Satoh Takao Fujii Satoshi Okabe 《Environmental microbiology》2015,17(6):2172-2189
To date, six candidate genera of anaerobic ammonium‐oxidizing (anammox) bacteria have been identified, and numerous studies have been conducted to understand their ecophysiology. In this study, we examined the physiological characteristics of an anammox bacterium in the genus ‘Candidatus Jettenia’. Planctomycete KSU‐1 was found to be a mesophilic (20–42.5°C) and neutrophilic (pH 6.5–8.5) bacterium with a maximum growth rate of 0.0020 h?1. Planctomycete KSU‐1 cells showed typical physiological and structural features of anammox bacteria; i.e. 29N2 gas production by coupling of 15NH4+ and 14NO2?, accumulation of hydrazine with the consumption of hydroxylamine and the presence of anammoxosome. In addition, the cells were capable of respiratory ammonification with oxidation of acetate. Notably, the cells contained menaquinone‐7 as a dominant respiratory quinone. Proteomic analysis was performed to examine underlying core metabolisms, and high expressions of hydrazine synthase, hydrazine dehydrogenase, hydroxylamine dehydrogenase, nitrite/nitrate oxidoreductase and carbon monoxide dehydrogenase/acetyl‐CoA synthase were detected. These proteins require iron or copper as a metal cofactor, and both were dominant in planctomycete KSU‐1 cells. On the basis of these experimental results, we proposed the name ‘Ca. Jettenia caeni’ sp. nov. for the bacterial clade of the planctomycete KSU‐1. 相似文献
106.
Multiplexin (Mp) is the Drosophila orthologue of vertebrate collagens XV and XVIII. Like them, Mp is widely distributed in the basement membranes of the developing embryos, including those of neuroblasts in the central and peripheral nervous systems, visceral muscles of the gut, and contractile cardioblasts. Here we report the identification of mutant larvae bearing piggyBac transposon insertions that exhibit decrease Mp production associated with abdominal cuticular and wing margin defects, malformation of sensory organs and impaired sensitivity to physical stimuli. Additional findings include the abnormal ultrastructure of fatbody associated with abnormal collagen IV deposition, and reduced Wingless deposition. Collectively, these findings are consistent with the notion that Mp is required for the proper formation and/or maintenance of basement membrane, and that Mp may be involved in establishing the Wingless signaling gradients in the Drosophila embryo. 相似文献
107.
Post-treatment of anaerobic wastewater was undertaken to biologically oxidize dissolved methane, with the aim of preventing methane emission. The performance of dissolved methane oxidation and competition for oxygen among methane, ammonium, organic matter, and sulfide oxidizing bacteria were investigated using a lab-scale closed-type down-flow hanging sponge (DHS) reactor. Under the oxygen abundant condition of a hydraulic retention time of 2h and volumetric air supply rate of 12.95m(3)-airm(-3)day(-1), greater than 90% oxidation of dissolved methane, ammonium, sulfide, and organic matter was achieved. With reduction in the air supply rate, ammonium oxidation first ceased, after which methane oxidation deteriorated. Sulfide oxidation was disrupted in the final step, indicating that COD and sulfide oxidation occurred prior to methane oxidation. A microbial community analysis revealed that peculiar methanotrophic communities dominating the Methylocaldum species were formed in the DHS reactor operation. 相似文献
108.
Tanabe G Otani T Cong W Minematsu T Ninomiya K Yoshikawa M Muraoka O 《Bioorganic & medicinal chemistry letters》2011,21(10):3159-3162
Four analogs with 3′-O-alkyl groups (9a: CH3, 9b: C2H5, 9c: C13H27 or 9d: CH2Ph) instead of the 3′-O-sulfate anion in salacinol (1), a naturally occurring potent α-glucosidase inhibitor, were synthesized by the coupling reaction of 1,4-dideoxy-1,4-epithio-d-arabinitols (18a and 18b) with appropriate epoxides (10a-10d). These analogs showed equal or considerably higher inhibitory activity against rat small intestinal α-glucosidases than the original sulfate (1), and one of them (9d) was found more potent than currently used α-glucosidase inhibitors as antidiabetics. Thus, introduction of a hydrophobic moiety at the C3′ position of this new class of inhibitor was found beneficial for onset of stronger inhibition against these enzymes. 相似文献
109.
110.
Tsunemi K Taguchi F Marutani M Watanabe-Sugimoto M Inagaki Y Toyoda K Shiraishi T Ichinose Y 《Molecular Plant Pathology》2011,12(7):709-714
The HrpZ harpin of Pseudomonas syringae is known to induce a hypersensitive response (HR) in some plants. In P. syringae pv. tabaci (Pta), the harpin gene hrpZ has been spontaneously disrupted by an internal deletion in its open reading frame and a frame shift. The loss of the ability of the recombinant harpin polypeptide of Pta to induce HR despite the high sensitivity of tobacco plants to harpin led us to investigate the meaning of the disrupted hrpZ gene in the virulence of Pta 6605. The hrpZ gene from P. syringae pv. pisi was introduced into wild-type (WT) Pta. The hrpZ-complemented Pta secreted harpin into the culture medium, but failed to cause disease symptoms by both infiltration and spray inoculation. Inoculation with the hrpZ-complemented Pta induced defence responses in tobacco plants, whereas the defence responses of tobacco plants were not prominent on inoculation with WT Pta. These results indicate that an ancestor of Pta might have disrupted hrpZ by an internal deletion to evade plant defences and confer the ability to cause disease in tobacco plants. 相似文献