全文获取类型
收费全文 | 939篇 |
免费 | 34篇 |
出版年
2021年 | 4篇 |
2019年 | 4篇 |
2018年 | 3篇 |
2017年 | 5篇 |
2016年 | 14篇 |
2015年 | 17篇 |
2014年 | 29篇 |
2013年 | 96篇 |
2012年 | 49篇 |
2011年 | 59篇 |
2010年 | 22篇 |
2009年 | 28篇 |
2008年 | 62篇 |
2007年 | 48篇 |
2006年 | 51篇 |
2005年 | 48篇 |
2004年 | 60篇 |
2003年 | 60篇 |
2002年 | 49篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 12篇 |
1998年 | 8篇 |
1997年 | 19篇 |
1996年 | 17篇 |
1995年 | 12篇 |
1994年 | 13篇 |
1993年 | 8篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 8篇 |
1988年 | 11篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 10篇 |
1984年 | 11篇 |
1983年 | 9篇 |
1982年 | 9篇 |
1981年 | 6篇 |
1980年 | 9篇 |
1979年 | 8篇 |
1978年 | 13篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 5篇 |
1974年 | 3篇 |
1973年 | 8篇 |
1972年 | 3篇 |
1970年 | 5篇 |
排序方式: 共有973条查询结果,搜索用时 15 毫秒
811.
Nakagawa K Ibusuki D Suzuki Y Yamashita S Higuchi O Oikawa S Miyazawa T 《Journal of lipid research》2007,48(12):2779-2787
We previously discovered that squalene monohydroperoxide (SQ-OOH) was produced on human forehead skin and suggested that skin squalene (SQ) may be the principal target lipid for oxidative stress (e.g., sunlight exposure). Because of its six double bonds, SQ peroxidation can yield various positional hydroperoxide isomers. However, the structural characterization of skin SQ-OOH isomers has never been reported. Here, we prepared pure SQ-OOH isomers and developed an analytical method for SQ-OOH isomers using a quadrupole/linear ion-trap mass spectrometer (QTRAP) MS/MS system. Collision-induced dissociation produced specific fragment ions for each SQ-OOH isomer, which permitted discrimination between SQ-OOH isomers by multiple reaction monitoring (MRM). When lipid extract from human forehead skin was subjected to LC-MS/MS with MRM, individual SQ-OOH isomers could be separated and detected with a sensitivity of 0.05 ng/injection. The total concentration of SQ-OOH isomers in forehead skin was approximately 956 microg/g skin lipids, but it increased up to 2,760 microg/g skin lipids after 3 h of sunlight exposure. The LC-MS/MS method was useful for investigating the peroxidation mechanisms of SQ as well as SQ-OOH-mediated skin disorders. 相似文献
812.
Artificial anti-cell death protein FNK, a Bcl-x(L) derivative with three amino acid-substitutions (Y22F, Q26N, and R165K) has enhanced anti-apoptotic and anti-necrotic activity and facilitates cell survival in many species and cell types. The objectives of this study were (i) to investigate whether the protein conjugated with a protein transduction domain (PTD-FNK) reduces myocardial infarct size and improves post-ischemic cardiac function in ischemic/reperfused rat hearts, and (ii) to understand the mechanism(s) by which PTD-FNK exerts a protective effect. Isolated rat hearts were subjected to 35-min global ischemia, followed by 120-min reperfusion using the Langendorff methods. PTD-FNK (a total of 30 microl) was injected intramuscularly into the anterior wall of the left ventricle either at 1 min after induction of global ischemia (group A) or at 30 min after induction of global ischemia (at 5 min before reperfusion) (group B). In group A, infarct size was significantly reduced from 47.8+/-6.8% in the control to 30.4+/-5.2, 28.7+/-3.8, and 30.4+/-6.8% with PTD-FNK at 5, 50, and 500 nmol/l, respectively (p<0.05). Temporal recovery of left ventricular developed pressure at 60 min and 120 min after reperfusion was significantly better in PTD-FNK (50 and 500 nmol/l)-treated groups than in the control (p<0.05). In contrast, PTD-FNK treatment had no effect on group B. Western blot analysis showed that PTD-FNK markedly inhibited procaspase-3 cleavage (activation of caspase-3) and reduced the number of nuclei stained by a terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphoshate nick-end labeling (TUNEL) assay. These findings suggest that PTD-FNK reduces the volume of myocardial infarction with corresponding functional recovery, at least in part, through the suppression of myocardial apoptosis following ischemia/reperfusion. 相似文献
813.
Globular adiponectin induces adhesion molecule expression through the sphingosine kinase pathway in vascular endothelial cells 总被引:3,自引:0,他引:3
Kase H Hattori Y Jojima T Okayasu T Tomizawa A Suzuki K Banba N Monden T Satoh H Akimoto K Kasai K 《Life sciences》2007,81(11):939-943
The signaling pathways that couple adiponectin receptors to functional, particularly inflammatory, responses have remained elusive. We report here that globular adiponectin induces endothelial cell activation, as measured by the expression of adhesion proteins such as vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin and MCP-1, through the sphingosine kinase (SKase) signaling pathway. Treatment of human umbilical vein endothelial cells with globular adiponectin resulted in NF-kappaB activation and increased mRNA levels of VCAM-1, ICAM-1, E-selectin and MCP-1. Sphingosine 1-phosphate (S1P), but not ceramide or sphingosine, was a potent stimulator of adhesion protein expression. As S1P is generated from sphingosine by SKase, we treated cells with siRNA for SKase to silence the effects of S1P in the endothelial cells. Treatment with SKase siRNA inhibited globular adiponectin-induced NF-kappaB activation and markedly decreased the globular adiponectin-induced mRNA levels of adhesion protein. Thus, we demonstrated that the SKase pathway, through the generation of S1P, is critically involved in mediating globular adiponectin-induced endothelial cell activation. 相似文献
814.
Akio Watanabe Momochika Kumagai Takashi Mishima Junya Ito Yurika Otoki Teppei Harada Tsuyoshi Kato Mikihiko Yoshida Misora Suzuki Izumi Yoshida Kazuhiro Fujita Masatoshi Watai Kiyotaka Nakagawa Teruo Miyazawa 《PloS one》2015,10(5)
Osteoporosis with bone loss is widely recognized as a major health problem. Bone homeostasis is maintained by balancing bone formation and bone resorption. The imbalance caused by increased bone resorption over bone formation can lead to various bone-related diseases such as osteoporosis and rheumatoid arthritis. Osteoclasts are the principal cells responsible for bone resorption and the main targets of anti-resorptive therapies. However, excessive inhibition of osteoclast differentiation may lead to inhibition of osteoblast differentiation. Therefore, it is important to screen for new compounds capable of inhibiting bone resorption and enhancing bone formation. Toddalia asiatica (L.) Lam. has been utilized traditionally for medicinal purposes such as the treatment of rheumatism. Currently, the extract is considered to be a good source of pharmacological agents for the treatment of bone-related diseases, but the active compounds have yet to be identified. We investigated whether toddaculin, derived from Toddalia asiatica (L.) Lam., affects both processes by inhibiting bone resorption and enhancing bone formation. Towards this end, we used pre-osteoclastic RAW 264 cells and pre-osteoblastic MC3T3-E1 cells. We found that toddaculin not only inhibited the differentiation of osteoclasts via activation of the NF-κB, ERK 1/2, and p38 MAPK signaling pathways, but it also induced differentiation and mineralization of osteoblasts by regulating differentiation factors. Thus, toddaculin might be beneficial for the prevention and treatment of osteoporosis. 相似文献
815.
Kumazawa Shuzo; Ogawa Teruo; Inoue Yorinao; Mitsui Akira 《Plant & cell physiology》1985,26(8):1485-1491
Whole cells of photoanaerobically grown Chromatium sp. strainMiami PBS 1071, a marine purple sulfur bacterium, oxidized H2in the dark through the oxyhydrogen reaction. Oxidation of H2was measured by injecting either H2 into an air-equilibratedcell suspension (microaerobic H2 oxidation) or O2 into an H2/Ar-equilibratedcell suspension (microaerobic H2 oxidation). Both types of H2oxidation were strongly inhibited by azide (40 mM), indicatingthat the oxidation proceeds via a terminal oxidase system. 2,5-Dibromo-3-methyl-6-isopropyl-p-benzoquinone(16 µM) inhibited aerobic H2 oxidation by 49% but it acceleratedmicroacrobic H2 oxidation. The sensitivity of H2 oxidation torotenone was higher under aerobic conditions. The results indicatethat H2 oxidation proceeds via two different pathways; one containsubiquinone and NAD, and the other does not. The contributionof each pathway depends on the O2 partial pressure.
4 Present address: Institute of Oceanic Research and Development,Tokai University, Shimizu, Shizuoka 424, Japan. (Received May 24, 1985; Accepted August 29, 1985) 相似文献
816.
Abstract Among 40 short rod-shaped mutants of Pseudomonas aeruginosa PAO isolated after nitrosoguanidine mutagenesis, a stable clone designated KG1034 was obtained and studied for its cellular and genetical features. Cells of the parent strain, PAO2302 had a mean cell length of 1.9 μm, whereas that of KG1034 was 1.3 μm. The doubling time of KG1034 was less than that of the parent strain, although both strains elongated at the same rate and exhibited the same relative amounts and pattern of penicillin-binding proteins. These results suggested that the phenotype of KG1034 was due to the initiation of septation at an earlier stage. The new gene responsible for this phenotype was named srs (abbreviation for short r od shape) and mapped by conjugation between cys -54 and puuC . 相似文献
817.
Intact chloroplasts were obtained from mesophyll protoplasts isolated from Mesembryanthemum crystallinum in the C3 or Crassulacean acid metabolism (CAM) photosynthetic mode, and examined for the influence of inorganic phosphate (Pi) on aspects of bicarbonate-dependent O2 evolution and CO2 fixation. While the chloroplasts from both modes responded similarly to varying Pi, some features appear typical of chloroplasts from species capable of CAM, including a relatively high capacity for photosynthesis in the absence of Pi, a short induction period, and resistance to inhibition of photosynthesis by high levels of Pi. In the absence of Pi the chloroplasts retained 75–85% of the 14CO2 fixed and the total export of dihydroxyacetone phosphate was low compared with the rate of photosynthesis. In CAM plants the ability to conduct photosynthesis and retain most of the fixed carbon in the chloroplasts at low external Pi concentrations may enable storage of carbohydrates which are essential for providing a carbon source for the nocturnal synthesis of malic acid. At high external Pi concentrations (e.g. 10 25 mM), the amount of total dihydroxyacetone phosphate exported to the assay medium relative to the rate of photosynthesis was high while the products of 14CO2 fixation were largely retained in the chloroplasts which indicates starch degradation is occurring at high Pi levels. Starch degradation normally occurs in CAM plants in the dark; high levels of Pi may induce starch degradation in the light which has the effect of limiting export of the immediate products of photosynthesis and thus the degree of Pi inhibition of photosynthesis with the isolated chloroplast. 相似文献
818.
Summary When Lactobacillus casei YIT 9018 (LC 9018) or Corynebacterium parvum, known to be immunomodulators possessing antitumor activity, were injected i.p. into BALB/c mice, peritoneal exudate macrophage Ia antigen detected by indirect immunofluorescence method was expressed on their cell surface, but it was not expressed following the injection of 10% proteose peptone, an inflammatory agent, or Lactobacillus fermentum YIT 0159 (LF 0159), which have no antitumor activity. The percentage and absolute number of Ia-positive peritoneal macrophages were maximum on the 7th day after the injection of LC 9018. Immunization by injection of Meth A fibrosarcoma cells treated with mitomycin C (MMC-Meth A) 7 days after LC 9018 injection suppressed the growth of Meth A implanted i.p. 14 days after MMC-Meth A injection. A shorter interval between the injections of LC 9018 and MMC-Meth A did not allow suppression of Meth A growth. These results showed that the increase in Ia-positive macrophages in the peritoneal cavity coincided with the effective interval for induction of the antitumor activity by LC 9018. The antitumor activity induced by injections of LC 9018 and MMC-Meth A did not affect the growth of RL l leukemic cells, syngeneic to BALB/c mice. Neutralization (Winn type) tests showed that peritoneal T lymphocytes possessed tumor cytotoxicity and that the antitumor capacity was reduced by in vivo treatment with anti I-Ad monoclonal antibody simultaneously with and 1 day prior to MMC-Meth A injection. These results indicate that LC 9018-induced Ia-positive macrophages, which first encounter a tumor antigen in the peritoneal cavity, play an important role in the in vivo induction of tumor specific T cell-mediated antitumor immunity. 相似文献
819.
Assay of 2-Hydroxyputrescine in Various Regions of Rat Brain by Gas Chromatography-Mass Spectrometry 总被引:1,自引:1,他引:0
Tadashi Noto Takeshi Hasegawa Hiromichi Hashimoto Teruo Nakajima 《Journal of neurochemistry》1988,50(2):464-467
2-Hydroxyputrescine in seven regions of single rat brains was measured with a sensitive, specific assay by gas chromatography-mass spectrometry. The regions were the cerebral cortex, cerebellum, medulla oblongata, hypothalamus, striatum, hippocampus, and midbrain. The level of 2-hydroxyputrescine was very high in the cerebral cortex and cerebellum, high in the medulla oblongata, hypothalamus, and hippocampus, and low in the striatum and midbrain. The level of 2-hydroxyputrescine in the cerebellum was significantly higher than in the striatum and midbrain. 相似文献
820.
Teruo Nishida Atsuko Ueda Masahiko Fukuda Hiroshi Mishima Kyoko Yasumoto Toshifumi Otori 《In vitro cellular & developmental biology. Plant》1988,24(10):1009-1014
Summary Corneal fibroblasts, also known as keratocytes are surrounded by an extracellular matrix of collagen in vivo. To understand
the physiology and pathology of these corneal fibroblasts, it is important to study their interactions with this extracellular
matrix. We cultured rabbit corneal fibroblasts on tissue culture plastic dishes or in a hydrated collagen gel and compared
the changes in morphology and mitotic activity. Corneal fibroblasts on plastic dishes were flattened and widely spread, whereas
those in collagen gel became spindle-shaped with long processes. Examination with an electron microscope revealed that the
corneal fibroblasts in collagen gel formed gap junctions with neighboring cells. Gap junctions were hardly ever observed between
corneal fibroblasts cultured on plastic dishes. Corneal fibroblasts cultured in a collagen matrix showed much less incorporation
of [3H]thymidine than did corneal fibroblasts cultured on plastic, and this incorporation decreased with increasing concentration
of collagen. Our present results suggest that the morphologic and biochemical characteristics of corneal fibroblasts cultured
in collagen gel are different from those cultured on plastic.
This research was supported in part by grants from the Ministry of Education, Science and Culture of Japan, by a grant from
Osaka Eye Bank, Osaka, Japan, and by an intramural research fund of Kinki University.
Part of this research was presented at the annual meeting of the Japanese Ophthalmological Society (May 1985) at Kyoto, Japan,
and at the annual meeting of the Association for Research in Vision and Ophthalmology (May 1987) at Sarasota, FL. 相似文献