全文获取类型
收费全文 | 1822篇 |
免费 | 104篇 |
国内免费 | 1篇 |
出版年
2022年 | 12篇 |
2021年 | 16篇 |
2020年 | 11篇 |
2019年 | 12篇 |
2018年 | 13篇 |
2017年 | 19篇 |
2016年 | 36篇 |
2015年 | 49篇 |
2014年 | 62篇 |
2013年 | 124篇 |
2012年 | 105篇 |
2011年 | 96篇 |
2010年 | 66篇 |
2009年 | 77篇 |
2008年 | 88篇 |
2007年 | 107篇 |
2006年 | 110篇 |
2005年 | 155篇 |
2004年 | 141篇 |
2003年 | 138篇 |
2002年 | 140篇 |
2001年 | 18篇 |
2000年 | 14篇 |
1999年 | 16篇 |
1998年 | 31篇 |
1997年 | 19篇 |
1996年 | 16篇 |
1995年 | 22篇 |
1994年 | 26篇 |
1993年 | 16篇 |
1992年 | 17篇 |
1991年 | 9篇 |
1990年 | 8篇 |
1989年 | 15篇 |
1988年 | 10篇 |
1987年 | 10篇 |
1986年 | 5篇 |
1985年 | 11篇 |
1984年 | 6篇 |
1983年 | 14篇 |
1982年 | 15篇 |
1981年 | 13篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 6篇 |
1970年 | 2篇 |
1959年 | 2篇 |
排序方式: 共有1927条查询结果,搜索用时 390 毫秒
921.
922.
Yuichi Koga Shigeki Sakamaki Mitsuya Hongu Eiji Kawanishi Toshiaki Sakamoto Yasuo Yamamoto Hirotaka Kimata Keiko Nakayama Chiaki Kuriyama Yasuaki Matsushita Kiichiro Ueta Minoru Tsuda-Tsukimoto Sumihiro Nomura 《Bioorganic & medicinal chemistry》2013,21(17):5561-5572
Canagliflozin (1), a novel inhibitor for sodium-dependent glucose cotransporter 2 (SGLT2), has been developed for the treatment of type 2 diabetes. To investigate the effect of replacement of the phenyl ring in 1 with heteroaromatics, C-glucosides 2 were designed, synthesized, and evaluated for their inhibitory activities against SGLT2. Of these, 3-pyridyl, 2-pyrimidyl or 5-membered heteroaryl substituted derivatives showed highly potent inhibitory activity against SGLT2, while 5-pyrimidyl substitution was associated with slightly reduced activity. In particular, 2g (TA-3404) had remarkable anti-hyperglycemic effects in high-fat diet fed KK (HF-KK) mice. 相似文献
923.
Wataru Kudo Ken-Ichi Yamada Yuichi Kinoshita Takeshi Shiba Toshiaki Watanabe 《Free radical research》2013,47(5):505-512
Nitroxyl radicals are important antioxidants that have been used to protect animal tissues from oxidative damage. Their reaction with hydroxyl radical (?OH) is generally accepted to be the mechanism of antioxidant function. However, the direct interaction of nitroxyl radicals with ?OH does not always provide a satisfactory explanation in various pH, because the concentration of hydrogen ion may affect the generation of secondary ?OH-derived radicals. In the present study, it was confirmed that the reaction between 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) and ?OH generated TEMPOL-hydroxylamine, 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPON) and TEMPON-hydroxylamine using HPLC coupled with electrochemical detection. In the absence of NADH, TEMPOL-H may be generated by the reaction with secondary ?OH-derived radicals in acidic condition. In the presence of NADH, a large proportion of the non-paramagnetic products was TEMPOL-H. Finally, it was clarified that TEMPOL-H was generated during dopamine metabolism, which is believed to be one of the ?OH sources in pathological processes such as Parkinson's disease. 相似文献
924.
925.
We previously demonstrated that the rice kinesin K16, which belongs to the kinesin-7 subfamily, has unique enzymatic properties and atomic structure within key functional regions. In this study, we focused on a novel rice plant kinesin, K23, which also belongs to the kinesin-7 subfamily. The biochemical characterization of the K23 motor domain (K23MD) was studied and compared with the rice kinesin K16 and other related kinesins. K23 exhibits ~45-fold (1.3 Pi mol(-1) site mol(-1) s(-1)) lower microtubule-dependent ATPase activity than conventional kinesins, whereas its affinity for microtubules is comparable with conventional kinesins. MgADP-free K23 is unstable compared with the unusually stable MgADP-free K16MD. The enzymatic properties of K23MD are somewhat different from those of K16. We used a fluorescent ATP analogue 2'(3')-O-(N'-methylanthraniloyl)-ATP (mant-ATP) for the kinetic characterization of K23. The fluorescence of mant-ATP was not significantly altered during its hydrolysis by K23. However, significant fluorescence resonance energy transfer (FRET) between mant-ATP and W21 in the motor domain was observed. The kinetic study using FRET revealed that K23 has unique kinetic characteristics when compared with other kinesins. 相似文献
926.
The arm light organ of the firefly squid, Watasenia scintillans, emits extremely bright flashes of light, which are caused by a luciferin-luciferase reaction involving ATP, Mg(2+) and molecular oxygen. The molecular mechanism underlying the bioluminescence reaction has remained unresolved, because the luciferase could not be identified or isolated. The arm light organ contains numerous rod-like bodies that are 2-6 μm long and 1-2 μm thick. This paper addresses the characterization of the extracted rod-like body. We found that the rod-like bodies emit the light in vitro by the luciferin-luciferase reaction. Furthermore, by using the X-ray powder diffraction method, we confirmed that the rod-like bodies are well-ordered microcrystals. 相似文献
927.
Fukumoto T Kano A Ohtani K Yamasaki-Kokudo Y Kim BG Hosotani K Saito M Shirakawa C Tajima S Izumori K Ohara T Shigematsu Y Tanaka K Ishida Y Nishizawa Y Tada Y Ichimura K Gomi K Akimitsu K 《Planta》2011,234(6):1083-1095
One of the rare sugars, D-allose, which is the epimer of D-glucose at C3, has an inhibitory effect on rice growth, but the molecular mechanisms of the growth inhibition by D-allose were unknown. The growth inhibition caused by D-allose was prevented by treatment with hexokinase inhibitors, D-mannoheptulose and N-acetyl-D-glucosamine. Furthermore, the Arabidopsis glucose-insensitive2 (gin2) mutant, which is a loss-of-function mutant of the glucose sensor AtHXK1, showed a D-allose-insensitive phenotype. D-Allose strongly inhibited the gibberellin-dependent responses such as elongation of the second leaf sheath and induction of α-amylase in embryo-less half rice seeds. The growth of the slender rice1 (slr1) mutant, which exhibits a constitutive gibberellin-responsive phenotype, was also inhibited by D-allose, and the growth inhibition of the slr1 mutant by D-allose was also prevented by D-mannoheptulose treatment. The expressions of gibberellin-responsive genes were down-regulated by D-allose treatment, and the down-regulations of gibberellin-responsive genes were also prevented by D-mannoheptulose treatment. These findings reveal that D-allose inhibits the gibberellin-signaling through a hexokinase-dependent pathway. 相似文献
928.
Kuroda E Antignano F Ho VW Hughes MR Ruschmann J Lam V Kawakami T Kerr WG McNagny KM Sly LM Krystal G 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(1):323-332
We report that SHIP(-/-) mice, compared to SHIP(+/+) mice, are Th2 skewed with elevated serum IgE and twice as many splenic CD4(+) Th2 cells that, when stimulated with anti-CD3, produce more IL-4 and less IFN-γ. Exploring the reason for this Th2 skewing, we found that freshly isolated SHIP(-/-) splenic and bone marrow basophils are present in elevated numbers and secrete far more IL-4 in response to IL-3 or to FcεRI stimulation than do WT basophils. These SHIP(-/-) basophils markedly skew wild-type macrophage colony stimulating factor-derived macrophages toward an M2 phenotype, stimulate OT-II CD4(+) Th cells to differentiate into Th2 cells, and trigger SHIP(+/+) B cells to become IgE-producing cells. All these effects are completely abrogated with neutralizing anti-IL-4 Ab. Exploring the cell signaling pathways responsible for hyperproduction of IL-4 by SHIP(-/-) basophils, we found that IL-3-induced activation of the PI3K pathway is significantly enhanced and that PI3K inhibitors, especially a p110α inhibitor, dramatically suppresses IL-4 production from these cells. In vivo studies, in which basophils were depleted from mast cell-deficient SHIP(+/+) and SHIP(-/-) mice, confirmed the central role that basophils play in the Th2 skewing of naive SHIP-deficient mice. Taken together, these studies demonstrate that SHIP is a potent negative regulator of IL-4 production from basophils and thus may be a novel therapeutic target for Th1- and Th2-related diseases. 相似文献
929.
Ito C Ohgimoto S Kato S Sharma LB Ayata M Komase K Takeuchi K Ihara T Ogura H 《Microbiology and immunology》2011,55(7):518-524
The Schwarz FF-8 (FF-8) and AIK-C measles virus vaccine strains are currently used for vaccination in Japan. Here, the complete genome nucleotide sequence of the FF-8 strain has been determined and its genome sequence found to be remarkably similar to that of the AIK-C strain. These two strains are differentiated only by two nucleotide differences in the phosphoprotein gene. Since the FF-8 strain does not possess the amino acid substitutions in the phospho- and fusion proteins which are responsible for the temperature-sensitivity and small syncytium formation phenotypes of the AIK-C strain, respectively, other unidentified common mechanisms likely attenuate both the FF-8 and AIK-C strains. 相似文献
930.
Mishima T Ito Y Hosono K Tamura Y Uchida Y Hirata M Suzsuki T Amano H Kato S Kurihara Y Kurihara H Hayashi I Watanabe M Majima M 《American journal of physiology. Heart and circulatory physiology》2011,300(2):H431-H439
It is known that the neural system plays a fundamental role in neovascularization. A neuropeptide, calcitonin gene-related peptide (CGRP), is widely distributed in the central and peripheral neuronal systems. However, it remains to be elucidated the role of CGRP in angiogenesis during ischemia. The present study examined whether endogenous CGRP released from neuronal systems facilitates revascularization in response to ischemia using CGRP knockout mice (CGRP-/-). CGRP-/- or their wild-type littermates (CGRP+/+) were subjected to unilateral hindlimb ischemia. CGRP-/- exhibited impaired blood flow recovery from ischemia and decreased capillary density expressed in terms of the number of CD-31-positive cells in the ischemic tissues compared with CGRP+/+. In vivo microscopic studies showed that the functional capillary density in CGRP-/- was reduced. Hindlimb ischemia increased the expression of pro-CGRP mRNA and of CGRP protein in the lumbar dorsal root ganglia. Lack of CGRP decreased mRNA expression of growth factors, including CD31, vascular endothelial growth factor-A, basic fibroblast growth factor, and transforming growth factor-β, in the ischemic limb tissue. The application of CGRP enhanced the mRNA expression of CD31 and VEGF-A in human umbilical vein endothelial cells (HUVECs) and fibroblasts. Subcutaneous infusion of CGRP8-37, a CGRP antagonist, using miniosmotic pumps delayed angiogenesis and reduced the expression of proangiogenic growth factors during hindlimb ischemia. These results indicate that endogenous CGRP facilitates angiogenesis in response to ischemia. Targeting CGRP may provide a promising approach for controlling angiogenesis related to pathophysiological conditions. 相似文献