全文获取类型
收费全文 | 12286篇 |
免费 | 654篇 |
国内免费 | 3篇 |
出版年
2022年 | 36篇 |
2021年 | 129篇 |
2020年 | 84篇 |
2019年 | 112篇 |
2018年 | 156篇 |
2017年 | 147篇 |
2016年 | 240篇 |
2015年 | 379篇 |
2014年 | 451篇 |
2013年 | 888篇 |
2012年 | 818篇 |
2011年 | 818篇 |
2010年 | 533篇 |
2009年 | 498篇 |
2008年 | 823篇 |
2007年 | 867篇 |
2006年 | 783篇 |
2005年 | 810篇 |
2004年 | 798篇 |
2003年 | 737篇 |
2002年 | 700篇 |
2001年 | 108篇 |
2000年 | 99篇 |
1999年 | 163篇 |
1998年 | 183篇 |
1997年 | 120篇 |
1996年 | 117篇 |
1995年 | 96篇 |
1994年 | 92篇 |
1993年 | 96篇 |
1992年 | 100篇 |
1991年 | 69篇 |
1990年 | 67篇 |
1989年 | 71篇 |
1988年 | 43篇 |
1987年 | 56篇 |
1986年 | 56篇 |
1985年 | 48篇 |
1984年 | 57篇 |
1983年 | 45篇 |
1982年 | 65篇 |
1981年 | 51篇 |
1980年 | 56篇 |
1979年 | 21篇 |
1978年 | 24篇 |
1977年 | 29篇 |
1976年 | 32篇 |
1975年 | 33篇 |
1974年 | 16篇 |
1973年 | 21篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Takashi Matozaki Yoji Murata Munemasa Mori Takenori Kotani Hideki Okazawa Hiroshi Ohnishi 《Cellular signalling》2010,22(12):1811-1817
The R3 subtype of receptor-type protein tyrosine phosphatases (RPTPs) includes VE-PTP, DEP-1, PTPRO, and SAP-1. All of these enzymes share a similar structure, with a single catalytic domain and putative tyrosine phosphorylation sites in the cytoplasmic region and fibronectin type III–like domains in the extracellular region. The expression of each R3 RPTP is largely restricted to a single or limited number of cell types, with VE-PTP and DEP-1 being expressed in endothelial or hematopoietic cells, PTPRO in neurons and in podocytes of the renal glomerulus, and SAP-1 in gastrointestinal epithelial cells. In addition, these RPTPs are localized specifically at the apical surface of polarized cells. The structure, expression, and localization of the R3 RPTPs suggest that they perform tissue-specific functions and that they might act through a common mechanism that includes activation of Src family kinases. In this review, we describe recent insights into R3-subtype RPTPs, particularly those of mammals. 相似文献
992.
Kobayashi Y Miyazawa M Kamei A Abe K Kojima T 《Bioscience, biotechnology, and biochemistry》2010,74(12):2385-2395
To determine the effects of mulberry (Morus alba L.) leaves on hyperlipidemia, we performed gene expression profiling of the liver. Rats were fed a high-fat diet and administered mulberry leaves for 7 weeks. Plasma triglyceride and non-esterified fatty acid levels were significantly lower in the rats treated with mulberry leaves as compared with the untreated rats. DNA microarray analysis revealed that mulberry leaves upregulated expression of the genes involved in α-, β- and ω-oxidation of fatty acids, mainly related to the peroxisome proliferator-activated receptor signaling pathway, and downregulated the genes involved in lipogenesis. Furthermore, treatment with mulberry leaves upregulated expression of the genes involved in the response to oxidative stress. These results indicate that consumption of fatty acids and inhibition of lipogenesis are responsible for the reduction in plasma lipids caused by mulberry administration. In addition, mulberry treatment maintains the body's oxidative state at a low level despite enhancing fatty acid oxidation. 相似文献
993.
Makoto Yamanaka Shigeki Nakamura Aiko Inoue Takashi Yasuda Yuichi Inoue Hiroharu Kawahara 《Cytotechnology》2010,62(4):287-291
Sodium butyrate (NaB) induced the membrane enclosed cell size vesicles from several IgM producing cell lines. We considered
the application of the cell-derived vesicles (CDVs) to drug delivery system (DDS) using the lung cancer specific IgM producing
AE6 cell line. Microscopic observation showed that the DiI fluorescence labeled AE6 vesicles were incorporated into the lung
cancer cell line A549. The anticancer drug, actinomycin D (actD), contained in AE6 and Ramos vesicles decreased the A549 cell
viability to 46 and 62% of control without actD, respectively. The cytotoxic effect in AE6 vesicles was superior to that in
the Ramos vesicles that have the lung cancer non-specific IgM on their surfaces. However, the result of the Ramos vesicles
suggests that the surface molecules other than IgM may interact with the A549 cells. In our method for vesicle production,
more specific and abundant antibodies mounted vesicles can be generated by transfection of their genes into cells followed
by NaB treatment. These suggest that the CDVs may be useful for the development of a drug carrier for DDS. 相似文献
994.
Irie K Furukawa S Kadono T Kawano T 《Zeitschrift für Naturforschung. C, Journal of biosciences》2010,65(11-12):681-687
Some hundred cells of Chlorella-like green algae are naturally enclosed within the cytoplasm of a single cell of green paramecia (Paramecium bursaria). Therefore, P. bursaria serves as an experimental model for studying the nature of endo-symbiosis made up through chemical communication between the symbiotic partners. For studying the mechanism of symbiotic regulations, the materials showing successful symbiosis are widely used. Apart from such successful model materials, some models for symbiotic distortion would be of great interest in order to understand the nature of successful symbiosis. Here, we describe a case of unsuccessful symbiosis causing unregulated growth of algae inside the hosting ciliates. Recently, we have screened some cell lines, from the mass of P. bursaria cells survived after paraquat treatment. The resultant cell lines (designated as KMZ series) show novel and unusual morphological features with heavily darker green colour distinguishable from the original pale green-coloured paramecia. In this type of isolates, endo-symbiotic algae are restricted within one or two dense spherical structures located at the center of the host cells' cytoplasm. Interestingly, this isolate maintains the host cells' circadian mating response which is known as an alga-dependent behaviour in the host cells. In contrast, we discuss that KMZ lacks the host-dependent regulation of algal growth, thus the algal complex often over-grows obviously exceeding the original size of the normal hosting ciliates. Additionally, possible use of this isolate as a novel model for symbiotic cell-to-cell communication is discussed. 相似文献
995.
Atsuzawa K Nakazawa A Mizutani K Fukasawa M Yamamoto N Hashimoto T Usuda N 《Histochemistry and cell biology》2010,134(6):565-579
The presence of a mitochondrial fatty acid β-oxidation system in the retina was shown by immunohistochemistry. Fatty acids
are considered to serve as a major energy source metabolized by fatty acid β-oxidation together with glucose metabolized by
glycolysis in the organs of the entire body, but almost nothing is known about this metabolic system in the retina. Adult
rat retinae were subjected to immunofluorescence and immuno-electron microscopy for the localization of fatty acid β-oxidation
enzymes, together with western blot analysis for quantitation of the amount of enzyme proteins and DNA microarray analysis
for gene expression. All the enzymes examined were shown to be present in the retina, but in small amounts, with the amount
of protein and gene expression in the retina being about 1/10 of those in the liver. Immunohistochemistry at light and electron
microscopic levels revealed the enzymes to be more preferentially localized to the mitochondria of Müller cells than the retinal
neurons. The Müller cells were isolated from the retina and confirmed for the presence of mitochondrial fatty acid β-oxidation
enzymes. A mitochondrial fatty acid β-oxidation system was thus shown to be present in the retina heterogeneously. 相似文献
996.
Osami Shoji Takashi Fujishiro Shingo Nagano Shota Tanaka Takuya Hirose Yoshitsugu Shiro Yoshihito Watanabe 《Journal of biological inorganic chemistry》2010,15(8):1331-1339
Cytochrome P450BSβ, a H2O2-dependent cytochrome P450 catalyzing the hydroxylation of long-alkyl-chain fatty acids, lacks the general acid–base residue
around the heme, which is indispensable for the efficient generation of the active species using H2O2. On the basis of the crystal structure of the palmitic acid bound form of cytochrome P450BSβ, it was suggested that the role of the general acid–base function was provided by the carboxylate group of fatty acids. The
participation of the carboxylate group of the substrate was supported by the fact that cytochrome P450BSβ can catalyze oxidations of nonnatural substrates such as styrene and ethylbenzene in the presence of a series of short-alkyl-chain
carboxylic acids as a dummy molecule of fatty acid. We refer to a series of short-alkyl-chain carboxylic acids as a “decoy
molecule”. As shown here, we have clarified the crystal structure of the decoy-molecule-bound form and elucidated that the
location of its carboxylate group is virtually the same as that of palmitic acid in the heme cavity, indicating that the carboxylate
group of the decoy molecule serves as the general acid–base catalyst. This result further confirms that the role of the acid–base
function is satisfied by the carboxylate group of the substrates. In addition, the structure analysis of the substrate-free
form has clarified that no remarkable structural change is induced by the binding of the decoy molecule as well as fatty acid.
Consequently, whether the carboxylate group is positioned in the active site provides the switching mechanism of the catalytic
cycle of cytochrome P450BSβ. 相似文献
997.
Jürgen Geisler Takashi Suzuki Hildegunn Helle Yasuhiro Miki Shuji Nagasaki Nhat K. Duong Dagfinn Ekse Turid Aas Dean B. Evans Per E. Lønning Hironobu Sasano 《The Journal of steroid biochemistry and molecular biology》2010,118(4-5):237-241
Breast cancer tissue estrogen levels on an average exceed plasma as well as benign breast tissue levels. To evaluate the contribution of intra-tumor aromatization to individual tumor estrogen levels (estradiol, E2; estrone, E1; estrone sulfate, E1S), breast cancer tissue sections obtained during mastectomy in 28 postmenopausal breast cancer patients were stained for aromatase protein expression using the aromatase antibody 677. The findings were correlated to intra-tumor estrogen levels determined with a highly sensitive HPLC-RIA. Staining with 677 alone (irrespective of the hormone receptor status) revealed no difference in tumor E2 levels comparing 677+ versus 677? tumors, although a non-significant trend towards higher tumor E1 and E1S levels was observed in 677+ breast cancers. In contrast, tumor levels of E2 were significantly higher in ER+ tumors compared to ER? tumors (P < 0.001) and to benign breast tissue from the same breast (P < 0.001). Analysing the additional effect of positive staining with the aromatase antibody 677 on tumor estrogen levels in the subgroup of ER+ tumors, revealed significantly higher tumor levels of E2 (mean level of 544.7 versus 197.1 fmol/g tissue) as well as a non-significant trend concerning tumor E1 (mean level of 296.9 versus 102.1 fmol/g tissue). The mean tumor tissue E1S level was observed somewhat lower in ER+677+ (103.5 fmol/g) versus ER+677? tumors (190.1 fmol/g). In the subgroup of ER+PgR+ tumors, tissue levels of E2 were also found to be significantly higher among 677+ compared to 677? tumors: 873.2 fmol/g (95% CI 395.9–1925.6) versus 217.9 fmol/g (95% CI 88.8–534.9) (P = 0.015).In conclusion, our results indicate a moderate effect of aromatase enzyme expression evaluated by IHC using the antibody 677 on intra-tumor estrogen levels among ER+ breast cancers. A substantial interindividual variation in the ratios between the individual estrogen fractions suggests additional effects, like alterations in other enzymes to be involved in the intra-tumor estrogen homeostasis. 相似文献
998.
Takashi L. Shimada Tomoo Shimada Ikuko Hara‐Nishimura 《The Plant journal : for cell and molecular biology》2010,61(3):519-528
The creation of transgenic plants has contributed extensively to the advancement of plant science. Establishing homozygous transgenic lines is time‐consuming and laborious, and using antibiotics or herbicides to select transformed plants may adversely affect the growth of some transgenic plants. Here we describe a novel technology, which we have named FAST (fluorescence‐accumulating seed technology), that overcomes these difficulties. Although this technology was designed for use in Arabidopsis thaliana, it may be adapted for use in other plants. The technology is based on the expression of a fluorescent co‐dominant screenable marker FAST, under the control of a seed‐specific promoter, on the oil body membrane. The FAST marker harbors a fusion gene encoding either GFP or RFP with an oil body membrane protein that is prominent in seeds. The marker protein was only expressed in a specific organ (i.e. in dry seeds) and at a specific time (i.e. during dormancy), which are desirable features of selectable and/or screenable markers. This technique provides an immediate and non‐destructive method for identifying transformed dry seeds. It identified the heterozygous transformed seeds among the T1 population and the homozygous seeds among the T2 population with a false‐discovery rate of <1%. The FAST marker reduces the length of time required to produce homozygous transgenic lines from 7.5 to 4 months. Furthermore, it does not require sterilization, clean‐bench protocols or the handling of large numbers of plants. This technology should greatly facilitate the generation of transgenic Arabidopsis plants. 相似文献
999.
Nobuhisa Ozaki Arigala Uma Ravi Sankar Mitsuji Yamashita Takashi Aoki Yasutaka Tanaka Motohiko Kimura Mitsuo Toda Michio Fujie Yasuo Takehara Harumi Sakahara 《Bioorganic & medicinal chemistry letters》2010,20(3):932-934
A new type of dendritic molecules Gd-DTPA-XDA-D1-Glc(OH), which work as a functionalized ligand coordinating gadolinium(III) ion at the center of their frameworks with two glucose moieties on the molecular surfaces, were readily synthesized with high yield. The structures were established by IR, 1H, 13C NMR, and mass spectral studies. Its bio-distribution patterns were evaluated on rats. 相似文献
1000.
Hirotoshi Urakawa Keiichi Yamada Keiko Komagoe Setsuko Ando Hiroyuki Oku Takashi Katsu Ichiro Matsuo 《Bioorganic & medicinal chemistry letters》2010,20(5):1771-1775
A series of cationic cyclic heptapeptides based on polymyxin B have been synthesized for use as permeabilizers of the outer membrane of Gram-negative bacteria. Only analogs with the Dab2-d-Phe3-Leu4-Xxx5 sequence (Xxx = Dab or Orn) showed a synergistic bactericidal effect when combined with conventional antibiotics, indicating that the Dab2 residue plays a critical role in permeation of the outer membrane of Gram-negative bacteria. 相似文献