全文获取类型
收费全文 | 2209篇 |
免费 | 127篇 |
国内免费 | 2篇 |
出版年
2023年 | 3篇 |
2022年 | 11篇 |
2021年 | 28篇 |
2020年 | 11篇 |
2019年 | 19篇 |
2018年 | 55篇 |
2017年 | 23篇 |
2016年 | 36篇 |
2015年 | 68篇 |
2014年 | 85篇 |
2013年 | 139篇 |
2012年 | 154篇 |
2011年 | 137篇 |
2010年 | 114篇 |
2009年 | 103篇 |
2008年 | 140篇 |
2007年 | 171篇 |
2006年 | 160篇 |
2005年 | 130篇 |
2004年 | 139篇 |
2003年 | 118篇 |
2002年 | 153篇 |
2001年 | 20篇 |
2000年 | 18篇 |
1999年 | 23篇 |
1998年 | 37篇 |
1997年 | 27篇 |
1996年 | 24篇 |
1995年 | 14篇 |
1994年 | 18篇 |
1993年 | 19篇 |
1992年 | 14篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 11篇 |
1988年 | 10篇 |
1987年 | 9篇 |
1986年 | 3篇 |
1985年 | 9篇 |
1984年 | 10篇 |
1983年 | 4篇 |
1982年 | 12篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1975年 | 5篇 |
1971年 | 3篇 |
1966年 | 2篇 |
1963年 | 2篇 |
排序方式: 共有2338条查询结果,搜索用时 203 毫秒
81.
82.
Ito S Ihara T Tamura H Tanaka S Ikeda T Kajihara H Dissanayake C Abdel-Motaal FF El-Sayed MA 《FEBS letters》2007,581(17):3217-3222
The tomato saponin alpha-tomatine has been proposed to kill sensitive cells by binding to cell membranes followed by leakage of cell components. However, details of the modes of action of the compound on fungal cells are poorly understood. In the present study, mechanisms involved in alpha-tomatine-induced cell death of fungi were examined using a filamentous pathogenic fungus Fusarium oxysporum. alpha-Tomatine-induced cell death of F. oxysporum (TICDF) occurred only under aerobic conditions and was blocked by the mitochondrial F(0)F(1)-ATPase inhibitor oligomycin, the caspase inhibitor D-VAD-fmk, and protein synthesis inhibitor cycloheximide. Fungal cells exposed to alpha-tomatine showed TUNEL-positive nuclei, depolarization of transmembrane potential of mitochondria, and reactive oxygen species (ROS) accumulation. These results suggest that TICDF occurs through a programmed cell death process in which mitochondria play a pivotal role. Pharmacological studies using inhibitors suggest that alpha-tomatine activates phosphotyrosine kinase and monomeric G-protein signaling pathways leading to Ca(2+) elevation and ROS burst in F. oxysporum cells. 相似文献
83.
Irikura D Inui T Beuckmann CT Aritake K Schreiber G Miyano M Inoue T Urade Y 《Journal of biochemistry》2007,141(2):173-180
Here we report the enzymatic and ligand-binding properties of a major secretory protein in the choroid plexus of cane toad, Bufo marinus, whose protein is homologous with lipocalin-type prostaglandin (PG) D synthase (L-PGDS) and is recombinantly expressed in Xenopus A6 cells and Escherichia coli. The toad protein bound all-trans retinal, bile pigment, and thyroid hormones with high affinities (K(d)=0.17 to 2.00 microM). The toad protein also catalysed the L-PGDS activity, which was accelerated in the presence of GSH or DTT, similar to the mammalian enzyme. The K(m) value for PGH(2) (17 microM) of the toad protein was almost the same as that of rat L-PGDS (14 microM), whereas the turnover number (6 min(-1)) was approximately 28 fold lower than that of rat L-PGDS. Site-directed mutagenesis based on a modeled structure of the toad protein revealed that Cys(59) and Thr(61) residues were crucial for the PGDS activity. The quadruple Gly(39)Ser/Ala(75)Ser/Ser(140)Thr/Phe(142)Tyr mutant of the toad protein, resembling mouse L-PGDS, showed a 1.6 fold increase in the turnover number and a shift in the optimum pH for the PGDS activity from 9.0 to 8.5. Our results suggest that the toad protein is a prototype of L-PGDS with a highly functional ligand-binding pocket and yet with a primitive catalytic pocket. 相似文献
84.
85.
Proteomic and microarray analyses of the Dictyostelium Zak1-GSK-3 signaling pathway reveal a role in early development
下载免费PDF全文
![点击此处可从《Eukaryotic cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Strmecki L Bloomfield G Araki T Dalton E Skelton J Schilde C Harwood A Williams JG Ivens A Pears C 《Eukaryotic cell》2007,6(2):245-252
GskA, the Dictyostelium GSK-3 orthologue, is modified and activated by the dual-specificity tyrosine kinase Zak1, and the two kinases form part of a signaling pathway that responds to extracellular cyclic AMP. We identify potential cellular effectors for the two kinases by analyzing the corresponding null mutants. There are proteins and mRNAs that are altered in abundance in only one or the other of the two mutants, indicating that each kinase has some unique functions. However, proteomic and microarray analyses identified a number of proteins and genes, respectively, that are similarly misregulated in both mutant strains. The positive correlation between the array data and the proteomic data is consistent with the Zak1-GskA signaling pathway's functioning by directly or indirectly regulating gene expression. The discoidin 1 genes are positively regulated by the pathway, while the abundance of the H5 protein is negatively regulated. Two of the targets, H5 and discoidin 1, are well-characterized markers for early development, indicating that the Zak1-GskA pathway plays a role in development earlier than previously observed. 相似文献
86.
87.
Maeda Yoshiaki Kobayashi Ryosuke Watanabe Kahori Yoshino Tomoko Bowler Chris Matsumoto Mitsufumi Tanaka Tsuyoshi 《Marine biotechnology (New York, N.Y.)》2022,24(4):788-800
Marine Biotechnology - Microalgae including diatoms are of interest for environmentally friendly manufacturing such as production of biofuels, chemicals, and materials. The highly oil-accumulating... 相似文献
88.
Tsuyoshi Kenri Yoshito Kawakita Hisashi Kudo U. Matsumoto Shigetarou Mori Yukio Furukawa Yuhei O. Tahara Keigo Shibayama Yuuki Hayashi Munehito Arai Makoto Miyata 《Biochemical and biophysical research communications》2019,508(4):1050-1055
Mycoplasma pneumoniae forms an attachment organelle at one cell pole, binds to the host cell surface, and glides via a unique mechanism. A 170-kDa protein, P1 adhesin, present on the organelle surface plays a critical role in the binding and gliding process. In this study, we obtained a recombinant P1 adhesin comprising 1476 amino acid residues, excluding the C-terminal domain of 109 amino acids that carried the transmembrane segment, that were fused to additional 17 amino acid residues carrying a hexa-histidine (6?×?His) tag using an Escherichia coli expression system. The recombinant protein showed solubility, and chirality in circular dichroism (CD). The results of analytical gel filtration, ultracentrifugation, negative-staining electron microscopy, and small-angle X-ray scattering (SAXS) showed that the recombinant protein exists in a monomeric form with a uniformly folded structure. SAXS analysis suggested the presence of a compact and ellipsoidal structure rather than random or molten globule-like conformation. Structure model based on SAXS results fitted well with the corresponding structure obtained with cryo-electron tomography from a closely related species, M. genitalium. This recombinant protein may be useful for structural and functional studies as well as for the preparation of antibodies for medical applications. 相似文献
89.
Hiroshi Hamajima Masaru Tanaka Miyuki Miyagawa Mayuko Sakamoto Tsuyoshi Nakamura Teruyoshi Yanagita 《Bioscience, biotechnology, and biochemistry》2019,83(8):1514-1522
ABSTRACTKoji, which is manufactured by proliferating non-pathogenic fungus Aspergillus oryzae on steamed rice, is the base for Japanese traditional fermented foods. We have revealed that koji and related Japanese fermented foods and drinks such as amazake, shio-koji, unfiltered sake and miso contain abundant glycosylceramide. Here, we report that feeding of koji glycosylceramide to obese mice alters the cholesterol metabolism . Liver cholesterol was significantly decreased in obese mice fed with koji glycosylceramide. We hypothesized that their liver cholesterol was decreased because it was converted to bile acids. Consistent with the hypothesis, many bile acids were increased in the cecum and feces of obese mice fed with koji glycosylceramide. Expressions of CYP7A1 and ABCG8 involved in the metabolism of cholesterol were significantly increased in the liver of mice fed with koji glycosylceramide. Therefore, it was considered that koji glycosylceramide affects the cholesterol metabolism in obese mice. 相似文献
90.
In myocardial cells (MCs), endothelin-1 (ET-1) exerts various effects such as hypertrophy, and causes cellular injury. Long-term treatment with an endothelin-A (ETA) receptor antagonist improves the survival of rats with heart failure, suggesting that myocardial endothelin system contributes to the progression of heart failure. p38 mitogen-activated kinase (MAPK) is a member of the MAPK family and activated by several forms of environmental stresses. We show here the effect of ET-1 on p38 MAPK activation and the role of ET-1-activated p38 MAPK on morphological changes in MCs. ET-1-stimulated p38 MAPK phosphorylation was detectable within 2 min and maximal at 5 min and was concentration dependent. The maximum effect was obtained at 10 nM. An ETA receptor antagonist, BQ-123, but not an endothelin-B receptor antagonist, BQ-788, inhibited these reactions. A p38 MAPK inhibitor, SB203580, failed to inhibit the morphological changes associated with ET-1-induced myocardial cell hypertrophy. These results indicate that p38 MAPK is activated by ET-1 but does not contribute to the development of ET-1-induced myocardial cell hypertrophy. 相似文献