全文获取类型
收费全文 | 1230篇 |
免费 | 89篇 |
出版年
2021年 | 11篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 9篇 |
2017年 | 15篇 |
2016年 | 13篇 |
2015年 | 34篇 |
2014年 | 38篇 |
2013年 | 59篇 |
2012年 | 53篇 |
2011年 | 62篇 |
2010年 | 44篇 |
2009年 | 32篇 |
2008年 | 62篇 |
2007年 | 56篇 |
2006年 | 59篇 |
2005年 | 49篇 |
2004年 | 61篇 |
2003年 | 59篇 |
2002年 | 49篇 |
2001年 | 41篇 |
2000年 | 46篇 |
1999年 | 50篇 |
1998年 | 15篇 |
1997年 | 15篇 |
1996年 | 13篇 |
1995年 | 10篇 |
1994年 | 14篇 |
1993年 | 13篇 |
1992年 | 34篇 |
1991年 | 28篇 |
1990年 | 33篇 |
1989年 | 31篇 |
1988年 | 19篇 |
1987年 | 32篇 |
1986年 | 14篇 |
1985年 | 21篇 |
1984年 | 13篇 |
1983年 | 13篇 |
1982年 | 9篇 |
1981年 | 11篇 |
1978年 | 6篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1974年 | 8篇 |
1973年 | 7篇 |
1972年 | 4篇 |
1971年 | 4篇 |
1969年 | 5篇 |
1967年 | 5篇 |
排序方式: 共有1319条查询结果,搜索用时 250 毫秒
991.
Kazumasa Aoyagi Kayo Akiyama Siranoush Shahrzad Chie Tomida Aki Hirayama Sohji Nagase Katsumi Takemura Akio Koyama Shoji Ohba Mitsuharu Narita 《Free radical research》1999,31(1):59-65
Guanidinosuccinic acid (GSA) is noted for its nitric oxide (NO) mimicking actions such as vasodilatation and activation of the N-methyl-D-aspartate (NMDA) receptor. We have reported that GSA is the product of argininosuccinate (ASA) and some reactive oxygen species, mainly the hydroxyl radical. We tested for GSA synthesis in the presence of NO donors. ASA (1 mM) was incubated with NOR-2, NOC-7 or 3-morpholinosydomine hydrochloride (SIN-1) at 37°C. GSA was determined by HPLC using a cationic resin for separation and phenanthrenequinone as an indicator. Neither NOR-2 or NOC-7 formed GSA. SIN-1, on the other hand, generates NO and the superoxide anion which, in turn, generated peroxynitrite which was then converted to the hydroxyl radical. Incubation of ASA with SIN-1 leads, via this route, to GSA. When ASA was incubated with 1 mM SIN-1, the amount of GSA produced depended on the incubation time and the concentration of ASA. Among the tested SIN-1 concentrations, from 0.5 to 5 mM, GSA synthesis was maximum at 0.5 mM and decreased with increasing concentrations of SIN-1. Carboxy-PTIO, a NO scavenger, completely inhibited GSA synthesis. SOD, a superoxide scavenger, decreased GSA synthesis by 20%, and catalase inhibited GSA synthesis only by 12%; DMSO, a hydroxyl radical scavenger completely inhibited GSA synthesis in the presence of SIN-1. These data suggest that the hydroxyl radical derived from a combination of NO and the superoxide anion generates GSA, a stable NO mimic. Meanwhile, synthesis of GSA by NO produces reactive oxygen and activates the NMDA receptor that generates NO from GSA, suggesting a positive feed back mechanism. 相似文献
992.
H Akiyama Y Hiraki M Noda C Shigeno H Ito T Nakamura 《The Journal of biological chemistry》1999,274(45):32192-32197
We cloned a cDNA encoding a novel mouse protein, named A-C1, by differential display between two mouse cell lines: embryonic fibroblast C3H10T1/2 and chondrogenic ATDC5. The deduced amino acid sequence of A-C1 consists of 167 amino acids and shows 46% identity with that of a ras-responsive gene, rat Ha-rev107. Northern blot analysis showed a distinct hybridization band of 3.2 kilobases. Expression of A-C1 mRNA was detected in undifferentiated ATDC5 cells and myoblastic C2C12 cells, while none of C3H10T1/2 cells, NIH3T3 fibroblasts, Balb/c 3T3 fibroblasts, osteoblastic MC3T3-E1 cells, and ST2 bone marrow stromal cells expressed A-C1 mRNA in vitro. Moreover, A-C1 mRNA was expressed in skeletal muscle, heart, brain, and bone marrow in adult mice. By in situ hybridization, A-C1 gene expression was localized in hippocampus as well as bone marrow cells. By immunocytochemistry, A-C1 protein was detected in the cytoplasm as well as perinuclear region of the cells. Transfection of A-C1 cDNA into Ha-ras-transformed NIH3T3 cell line caused increase in the number of flat colonies and inhibition of cell growth. Our data indicate that A-C1 is expressed in some specific tissues in vivo and modulates Ha-ras-mediated signaling pathway. 相似文献
993.
Generation of thromboxane A2 from highly purified human sinus mast cells after immunological stimulation. 总被引:1,自引:0,他引:1
H Mita T Ishii K Akiyama 《Prostaglandins, leukotrienes, and essential fatty acids》1999,60(3):175-180
To better understand metabolites of arachidonic acid generated from human mast cells, the present study assessed the capacity of human mast cells to synthesize thromboxane B2 (TXB2). Anti-IgE challenge of human sinus mast cells resulted in the generation of TXB2 in a dose-dependent manner with a maximal generation of 8.2+/-4.4 ng/10(6) cells (n = 12), which is about 10-fold lower than the maximal generation of prostaglandin D2 (PGD2). Pretreatment of the cells with OKY-046, an inhibitor of TXA synthase, prevented formation of TXB2 in a dose-dependent manner without affecting the generation of PGD2 or leukotriene C4. Experiments using indomethacin or MK-591, a potent FLAP inhibitor, showed that shunting of arachidonic acid did not occur in a single-cell suspension of mast cells. Analysis by RT-PCR revealed that two species of TXA synthase, the full-length TXA synthase mRNA (TXAS-1, 570 BP) and a small quantity of the alternate-spliced form (400 BP), were present in mast cells. When cellular levels of TXAS-1 mRNA were normalized to those of G3PDH mRNA, the relative concentration of TXAS-1 was 2.06+/-0.60 (n = 7) in highly purified sinus mast cells (92.3+/-3.0% pure) and 3.66+/-0.98 (n = 5) in eosinophils. 相似文献
994.
H Kogen K Tago M Arai E Minami K Masuda T Akiyama 《Bioorganic & medicinal chemistry letters》1999,9(10):1347-1350
Practical and highly stereoselective synthesis of diterpene alcohol, plaunotol (1) and its thiourea derivatives 2a, 3a and 4a, via Z-selective Wittig reaction between alpha-acetal ketone 5 and phosphonium salt 6 and their antibacterial activity against Helicobacter pylori are described. 相似文献
995.
Takuji Kawamura Zsolt Radak Hiroki Tabata Hiroshi Akiyama Nobuhiro Nakamura Ryoko Kawakami Tomoko Ito Chiyoko Usui Matyas Jokai Ferenc Torma Hyeon-Ki Kim Motohiko Miyachi Suguru Torii Katsuhiko Suzuki Kaori Ishii Shizuo Sakamoto Koichiro Oka Mitsuru Higuchi Isao Muraoka Kristen M. McGreevy Steve Horvath Kumpei Tanisawa 《Aging cell》2024,23(1):e13960
DNA methylation-based age estimators (DNAm ageing clocks) are currently one of the most promising biomarkers for predicting biological age. However, the relationships between cardiorespiratory fitness (CRF), measured directly by expiratory gas analysis, and DNAm ageing clocks are largely unknown. We investigated the relationships between CRF and the age-adjusted value from the residuals of the regression of DNAm ageing clock to chronological age (DNAmAgeAcceleration: DNAmAgeAccel) and attempted to determine the relative contribution of CRF to DNAmAgeAccel in the presence of other lifestyle factors. DNA samples from 144 Japanese men aged 65–72 years were used to appraise first- (i.e., DNAmHorvath and DNAmHannum) and second- (i.e., DNAmPhenoAge, DNAmGrimAge, and DNAmFitAge) generation DNAm ageing clocks. Various surveys and measurements were conducted, including physical fitness, body composition, blood biochemical parameters, nutrient intake, smoking, alcohol consumption, disease status, sleep status, and chronotype. Both oxygen uptake at ventilatory threshold (VO2/kg at VT) and peak oxygen uptake (VO2/kg at Peak) showed a significant negative correlation with GrimAgeAccel, even after adjustments for chronological age and smoking and drinking status. Notably, VO2/kg at VT and VO2/kg at Peak above the reference value were also associated with delayed GrimAgeAccel. Multiple regression analysis showed that calf circumference, serum triglyceride, carbohydrate intake, and smoking status, rather than CRF, contributed more to GrimAgeAccel and FitAgeAccel. In conclusion, although the contribution of CRF to GrimAgeAccel and FitAgeAccel is relatively low compared to lifestyle-related factors such as smoking, the results suggest that the maintenance of CRF is associated with delayed biological ageing in older men. 相似文献
996.
Naotaka Kuroda Kenichiro Nakashima Shuzo Akiyama Naofumi Sato Noriko Imi Kamon Shirakawa Akio Uemura 《Luminescence》1998,13(1):25-29
A chemiluminescence (CL) determination of adenyl compounds is described. CL derivatization of adenyl compounds with methylglyoxal dimethyl acetal was performed in the presence of tungstosilicic acid and propan-2-ol. CL from adenyl compounds was produced by hydrogen peroxide and L -cysteine ethyl ester in DMF and water. The proposed method is highly sensitive and specific to compounds containing adenine. Adenine was determined in the range 1.0 × 10−3 −5.0 × 10−8 M with the detection limit of 3.0 × 10−8 M (150 fmol per assay). The method was applied to the determination of DNA and detection limits of a few nanograms of DNA achieved. © 1998 John Wiley & Sons, Ltd. 相似文献
997.
Mitsuhiro Wada Kenichiro Nakashima Naotaka Kuroda Shuzo Akiyama Kazuhiro Imai 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1996,678(2):129
A sensitive and rapid flow-injection analysis (FIA) of total choline-containing phospholipids (PLs) and a selective FIA method for the class assay of choline-containing PLs combined with preparative HPLC were described. The FIA method is based on peroxyoxaxalate chemiluminescence (PO-CL) detection of hydrogen peroxide enzymatically formed from choline-containing PL. The linear standard curves were obtained up to 1 nmol/20-μl injection (r>0.999) with the detection limits of 1.3–1.6 pmol at a signal-to-noise ratio of 2. The total amounts of choline-containing PLs in human serum were ranged from 1.63 to 3.19 mg/ml. The HPLC separation of choline-containing PLs was achieved with an aminopropyl-modified silica gel column using a mixture of acetonitrile-methanol-10 mM ammonium phosphate buffer pH 5.8 as eluent. The eluate corresponding to each choline-containing PL was collected, evaporated, dissolved in 0.1% Triton X-100 aqueous solution, and then injected into FIA system. The FIA method combined with preparative HPLC was applied to the assay of human serum. 相似文献
998.
Mitsumasa Akiyama Hodaka Sugimoto Shin-ichiro Inoue Yohei Takahashi Maki Hayashi Yuki Hayashi Miya Mizutani Takumi Ogawa Daichi Kinoshita Eigo Ando Meeyeon Park William M Gray Toshinori Kinoshita 《Plant physiology》2022,188(4):2228
Plasma membrane (PM) H+-ATPase in guard cells is activated by phosphorylation of the penultimate residue, threonine (Thr), in response to blue and red light, promoting stomatal opening. Previous in vitro biochemical investigation suggested that Mg2+- and Mn2+-dependent membrane-localized type 2C protein phosphatase (PP2C)-like activity mediates the dephosphorylation of PM H+-ATPase in guard cells. PP2C clade D (PP2C.D) was later demonstrated to be involved in PM H+-ATPase dephosphorylation during auxin-induced cell expansion in Arabidopsis (Arabidopsis thaliana). However, it is unclear whether PP2C.D phosphatases are involved in PM H+-ATPase dephosphorylation in guard cells. Transient expression experiments using Arabidopsis mesophyll cell protoplasts revealed that all PP2C.D isoforms dephosphorylate the endogenous PM H+-ATPase. We further analyzed PP2C.D6/8/9, which display higher expression levels than other isoforms in guard cells, observing that pp2c.d6, pp2c.d8, and pp2c.d9 single mutants showed similar light-induced stomatal opening and phosphorylation status of PM H+-ATPase in guard cells as Col-0. In contrast, the pp2c.d6/9 double mutant displayed wider stomatal apertures and greater PM H+-ATPase phosphorylation in response to blue light, but delayed dephosphorylation of PM H+-ATPase in guard cells; the pp2c.d6/8/9 triple mutant showed similar phenotypes to those of the pp2c.d6/9 double mutant. Taken together, these results indicate that PP2C.D6 and PP2C.D9 redundantly mediate PM H+-ATPase dephosphorylation in guard cells. Curiously, unlike auxin-induced cell expansion in seedlings, auxin had no effect on the phosphorylation status of PM H+-ATPase in guard cells.Type 2C protein phosphatase clade D family members redundantly dephosphorylate the penultimate C-terminal threonine residue of plasma membrane H+-ATPase in guard cells to control stomatal movement. 相似文献
999.
We have performed an immunocytochemical study of peptidylarginine deiminase (EC 3.5.3.15) in various rat tissues using an antiserum to the enzyme purified from rat skeletal muscle. Staining was observed in skeletal muscle fibers, glia cells of the central nervous system, serous cells of submandibular gland, demilunar cells (serous cells) of sublingual gland, uterine endometrium and myometrium, and certain cells in the lamina propria of intestinal villi. Possible involvement of the enzyme in multiple cellular processes were discussed. 相似文献
1000.
The chymotrypsin-like activity of human prostate-specific antigen, gamma-seminoprotein 总被引:4,自引:0,他引:4
gamma-Seminoprotein (gamma-Sm) is a human prostate-specific antigen and a serine protease judging from the complete amino acid sequence which shows extensive homology with the kallikrein family. The enzymatic activity of gamma-Sm was defined as a chymotrypsin-like activity using reduced and S-3-(trimethylated amino)propylated lysozyme and insulin-oxidized A and B chains as substrates. The -Leu/Ser- peptide bond of lysozyme was rapidly hydrolyzed by gamma-Sm. gamma-Sm also hydrolyzed the -Phe/Glu- of lysozyme and the -Leu/Cys(SO3H)- of insulin B chain. Insulin A chain and arginyl- or lysyl-linkage of these proteins were not hydrolyzed by gamma-Sm at all. 相似文献