全文获取类型
收费全文 | 2767篇 |
免费 | 130篇 |
国内免费 | 2篇 |
出版年
2022年 | 10篇 |
2021年 | 34篇 |
2020年 | 18篇 |
2019年 | 26篇 |
2018年 | 37篇 |
2017年 | 30篇 |
2016年 | 49篇 |
2015年 | 81篇 |
2014年 | 86篇 |
2013年 | 155篇 |
2012年 | 136篇 |
2011年 | 171篇 |
2010年 | 116篇 |
2009年 | 91篇 |
2008年 | 190篇 |
2007年 | 163篇 |
2006年 | 157篇 |
2005年 | 147篇 |
2004年 | 157篇 |
2003年 | 142篇 |
2002年 | 128篇 |
2001年 | 40篇 |
2000年 | 54篇 |
1999年 | 44篇 |
1998年 | 41篇 |
1997年 | 45篇 |
1996年 | 29篇 |
1995年 | 47篇 |
1994年 | 22篇 |
1993年 | 31篇 |
1992年 | 34篇 |
1991年 | 37篇 |
1990年 | 43篇 |
1989年 | 28篇 |
1988年 | 30篇 |
1987年 | 29篇 |
1986年 | 24篇 |
1985年 | 23篇 |
1984年 | 19篇 |
1983年 | 11篇 |
1982年 | 18篇 |
1981年 | 20篇 |
1980年 | 12篇 |
1979年 | 11篇 |
1978年 | 17篇 |
1977年 | 12篇 |
1976年 | 6篇 |
1973年 | 8篇 |
1971年 | 6篇 |
1970年 | 5篇 |
排序方式: 共有2899条查询结果,搜索用时 15 毫秒
121.
Shigemitsu Matsumoto Naoki Miyamoto Takaharu Hirayama Hideyuki Oki Kengo Okada Michiko Tawada Hidehisa Iwata Kazuhide Nakamura Seiji Yamasaki Hiroshi Miki Akira Hori Shinichi Imamura 《Bioorganic & medicinal chemistry》2013,21(24):7686-7698
To identify compounds with potent antitumor efficacy for various human cancers, we aimed to synthesize compounds that could inhibit c-mesenchymal epithelial transition factor (c-Met) and vascular endothelial growth factor receptor 2 (VEGFR2) kinases. We designed para-substituted inhibitors by using co-crystal structural information from c-Met and VEGFR2 in complex with known inhibitors. This led to the identification of compounds 3a and 3b, which were capable of suppressing both c-Met and VEGFR2 kinase activities. Further optimization resulted in pyrazolone and pyridone derivatives, which could form intramolecular hydrogen bonds to enforce a rigid conformation, thereby producing potent inhibition. One compound of particular note was the imidazo[1,2-a]pyridine derivative (26) bearing a 6-methylpyridone ring, which strongly inhibited both c-Met and VEGFR2 enzyme activities (IC50 = 1.9, 2.2 nM), as well as proliferation of c-Met-addicted MKN45 cells and VEGF-stimulated human umbilical vein endothelial cells (IC50 = 5.0, 1.8 nM). Compound 26 exhibited dose-dependent antitumor efficacy in vivo in MKN45 (treated/control ratio [T/C] = 4%, po, 5 mg/kg, once-daily) and COLO205 (T/C = 13%, po, 15 mg/kg, once-daily) mouse xenograft models. 相似文献
122.
Ari Dwi Nugraheni Satoshi Nagao Sachiko Yanagisawa Takashi Ogura Shun Hirota 《Journal of biological inorganic chemistry》2013,18(3):383-390
We have previously shown that methionine–heme iron coordination is perturbed in domain-swapped dimeric horse cytochrome c. To gain insight into the effect of methionine dissociation in dimeric cytochrome c, we investigated its interaction with cyanide ion. We found that the Soret and Q bands of oxidized dimeric cytochrome c at 406.5 and 529 nm redshift to 413 and 536 nm, respectively, on addition of 1 mM cyanide ion. The binding constant of dimeric cytochrome c and cyanide ion was obtained as 2.5 × 104 M?1. The Fe–CN and C–N stretching (ν Fe–CN and ν CN) resonance Raman bands of CN?-bound dimeric cytochrome c were observed at 443 and 2,126 cm?1, respectively. The ν Fe–CN frequency of dimeric cytochrome c was relatively low compared with that of other CN?-bound heme proteins, and a relatively strong coupling between the Fe–C–N bending and porphyrin vibrations was observed in the 350–450-cm?1 region. The low ν Fe–CN frequency suggests weaker binding of the cyanide ion to dimeric cytochrome c compared with other heme proteins possessing a distal heme cavity. Although the secondary structure of dimeric cytochrome c did not change on addition of cyanide ion according to circular dichroism measurements, the dimer dissociation rate at 45 °C increased from (8.9 ± 0.7) × 10?6 to (3.8 ± 0.2) × 10?5 s?1, with a decrease of about 2 °C in its dissociation temperature obtained with differential scanning calorimetry. The results show that diatomic ligands may bind to the heme iron of dimeric cytochrome c and affect its stability. 相似文献
123.
A new growth inhibitant against hiochi-bacteria, C11H18N2O, m.p. 173~4°C, named muta-aspergillic acid, has been isolated from the crystals of crude hydroxyaspergillic acid, obtained from culture filtrate of Asp. oryzae. Successful separation of these two compounds from each other was accomplished by counter current distribution method. The physical and chemical properties of muta-aspergillic acid as well as its physiological properties are described. 相似文献
124.
Tamo Fukamizo Kouji Sonoda Hideyoshi Toyoda Seiji Ouchi Sachio Goto 《Bioscience, biotechnology, and biochemistry》2013,77(10):2761-2762
An abdominal fat accumulation complicated by high blood triglycerides is regarded as a risk factor of metabolic syndrome. Feeding powdered nacre, mother of pearl, from Pinctada maxima, resulted in reduced body weight, visceral fat amount, and blood triglyceride level without influencing the food intake, body length, or amount of muscular tissue, suggesting that nacre powder specifically could decrease visceral fat. 相似文献
125.
Several analogs of abscisic acid (ABA) were prepared and their biological activities were assayed. Among the compounds tested, 5-(l, 2-epoxy-2, 6, 6-trimethyl-l-cyclohexyl)-, 5-(l-hydroxy-2, 6, 6-trimethyl-2-cyclohexen-l-yl)- and 5-(l-hydroxy-2-methylene-6, 6-dimethyl-l-cyclohexyl)-3-methyl-cis, trans-2, 4-pentadienoic esters (V, IX, XXIII and XXV) were found to be potent plant growth inhibitors. Their activities were superior or comparable to that of ABA. 相似文献
126.
Hironobu Iinuma Naomasa Yagisawa Seiji Shibahara Yasuji Suhara Shinichi Kondo Kenji Maeda 《Bioscience, biotechnology, and biochemistry》2013,77(11):2099-2105
Dopastin, an inhibitor of dopamine β-hydroxylase of microbial origin, was shown to be N-[2(S)-nitrosohydroxylamino-3-methylbutyl] crotonamide based on chemical, spectroscopic and synthetic studies. The total synthesis of dopastin was completed in 8 steps starting from l-valinol. N-Nitrosohydroxylamino function was introduced through an oxaziran with retention of the absolute configuration in the final product. Thus, the 2S-configuration of dopastin was proved by the total synthesis. Racemic dopastin was also synthesized from isobutyraldehyde in 7 steps. 相似文献
127.
Toshiake Matsuzaki Akira Koiwai Teruyoshi Nagao Fumihiko Sato Yasuyuki Yamada 《Bioscience, biotechnology, and biochemistry》2013,77(7):1699-1706
Among photomixotrophic green calluses tested (N. rustica. N. tobacum L. cv. BY-4 and Samsun), the callus of Samsun had the highest contents of chlorophyll and chloroplast lipids, such as monogalactosyldiglyceride (MGDG), digalactosyldiglyceride (DGDG), sulfoquinovosyldigly-ceride (SQDG) and phosphatidylglycerol (PG). However, the chlorophyll and chloroplast lipids in the green callus of Samsun were still 1/6 and 1/3 of that in the parent leaves, respectively. The relative content of a-linolenate in MGDG, DGDG and SQDG of the green calluses were higher than that of the white calluses. The ratios of hexadecatrienoate in MGDG and hexadeceno-ate (Δ3-trans) in PG in the green calluses were trace or less compared with that of the parent leaves. The crude lipids and total fatty acid contents of the chlorophyll deficient leaves (N. taba-cum L. cv. Consolation 402 and Dominant Aurea Su/su) were almost the same as those of the normal leaves (cv. BY-4 and Samsun), although the chlorophyll contents of the chlorophyll deficient leaves were 1/3 ~ 1/4 of that of the normal leaves. The ratios of chloroplast lipids in the total polar lipids in the chlorophyll deficient leaves were a little lower than that in the normal green leaves, but the former had a slightly higher ratio of phospholipids such as phosphatidylcholine and phosphatidylethanolamine than the latter. There were few differences in the fatty acid compositions of each individual lipid betweeen both types of leaves. 相似文献
128.
Cell protein isolates were prepared from yeast (S. cerevisiae) by alkali-extraction followed by acid precipitation. The relationships between alkali-treatment and nucleic acid contents in cell protein isolates were examined.The isolate which was precipitated at pH 4.5 following extraction with 0.20 n NaOH at 80°C contained small amounts (less than 1 % of the isolate) of nucleic acids. However, the content of nucleotides in the isolate which was precipitated at pH 4.5 following extraction with 0.20 n NaOH at 37°C was 9.13% of the product. Treatment by washing or dialysis of the isolate had little effect in removing the nucleotides in the isolate.This finding was explained by the interaction of nucleotide to cell protein isolate. The binding energy was measured by Hummel’s method. 相似文献
129.
Ling Xu Megumi Kanasaki Jianhua He Munehiro Kitada Kenji Nagao Hiroko Jinzu Yasushi Noguchi Hiroshi Maegawa Keizo Kanasaki Daisuke Koya 《生物化学与生物物理学报:疾病的分子基础》2013,1832(10):1605-1612
Ketogenic amino acid (KAA) replacement diet has been shown to cure hepatic steatosis, a serious liver disease associated with diverse metabolic defects. In this study, we investigated the effects of KAA replacement diet on nutrition sensing signaling pathway and analyzed whether induction of hepatic autophagy was involved. Mice are fed with high fat diet (HFD) or KAA replacement in high-fat diet (30% fat in food; HFD)-fed (HFDKAAR) and sacrificed at 8, 12, 16 weeks after initiation of experimental food. Hepatic autophagy was analyzed in protein expression of several autophagy-associated molecules and in light chain-3 green fluorescent protein (LC-3 GFP) transgenic mice. HFDKAAR showed increased AMP-activated protein kinase (AMPK) phosphorylation and enhanced liver kinase B1 (LKB1) expression compared to control HFD-fed mice. The KAA-HFD-induced activation of AMPK was associated with an increased protein expression of sirtuin 1 (Sirt1), decreased forkhead box protein O3a (Foxo3a) level, and suppression of mammalian target of rapamycin (mTOR) phosphorylation compared with the HFD-fed mice. The intervention study revealed that a KAA-replacement diet also ameliorated all the established metabolic and autophagy defects in the HFD-fed mice, suggesting that a KAA-replacement diet can be used therapeutically in established diseases. These results indicate that KAA replacement in food could be a novel strategy to combat hepatic steatosis and metabolic abnormalities likely involvement of an induction of autophagy. 相似文献
130.
Toshiaki Nakano Rikiya Kamei Takashi Fujimura Yuki Takaoka Ayane Hori Chia-Yun Lai Kuei-Chen Chiang Yayoi Shimada Naoya Ohmori Takeshi Goto Kazuhisa Ono Chao-Long Chen Shigeru Goto Seiji Kawamoto 《PloS one》2016,11(4)
Nuclear antigens are known to trigger off innate and adaptive immune responses. Recent studies have found that the complex of nucleic acids and core histones that are derived from damaged cells may regulate allergic responses. However, no fundamental study has been performed concerning the role of linker histone H1 in mast cell-mediated type I hyperreactivity. In this study, we explored the impact of histone H1 on mast cell-mediated allergic responses both in vitro and in vivo. In the course of a bona-fide experimental allergen sensitization model upon co-injection with alum adjuvant, ovalbumin (OVA), but not PBS, induced elevated levels of circulating histone H1. Intranasal challenge with histone H1 to OVA/alum- (but not PBS/alum)-sensitized mice induced significantly severer symptoms of allergic rhinitis than those in mice sensitized and challenged with OVA. A monoclonal antibody against histone H1 not only suppressed mast cell degranulation, but also ameliorated OVA-induced nasal hyperreactivity and IgE-mediated passive cutaneous anaphylaxis. Our present data suggest that nuclear histone H1 represents an alarmin-like endogenous mediator acting on mast cells, and that its blockage has a therapeutic potential for mast cell-mediated type I hyperreactivity. 相似文献