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41.
Y Takahashi T Koyanagi Y Suzuki Y Saga N Kanomata T Moriya M Suzuki Y Sato 《Molecular cancer research : MCR》2012,10(9):1135-1146
Vasohibin-1 (VASH1) is a VEGF-inducible endothelium-derived angiogenesis inhibitor and VASH2 is its homolog. Our previous analysis revealed that VASH1 is expressed in endothelial cells to terminate angiogenesis, whereas VASH2 is expressed in infiltrating mononuclear cells mobilized from bone marrow to promote angiogenesis in a mouse model of hypoxia-induced subcutaneous angiogenesis. To test the possible involvement of VASH2 in the tumor, we examined human ovarian cancer cells for the presence of VASH2. Immunohistochemical analysis revealed that VASH2 protein was preferentially detected in cancer cells of serous ovarian adenocarcinoma. We then used SKOV-3 and DISS, two representative human serous adenocarcinoma cell lines, and examined the role of VASH2 in the tumor. The knockdown of VASH2 showed little effect on the proliferation of cancer cells in vitro but notably inhibited tumor growth, peritoneal dissemination, and tumor angiogenesis in a murine xenograft model. Next, we stably transfected the human VASH2 gene into two types of murine tumor cells, EL-4 and MLTC-1, in which endogenous VASH2 was absent. When either EL-4 or MLTC-1 cells were inoculated into VASH2 (-/-) mice, the VASH2 transfectants formed bigger tumors when compared with the controls, and the tumor microvessel density was significantly increased. VASH2 stimulated the migration of endothelial cells, and its increased expression in cancer cells is related to the decrease of mir-200b. These results indicate that VASH2 expressed in serous ovarian carcinoma cells promoted tumor growth and peritoneal dissemination by promoting angiogenesis. Mol Cancer Res; 10(9); 1135-46. ?2012 AACR. 相似文献
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Daniel C Hatton Qi Yue Jacqueline Dierickx Chantal Roullet Keiichi Otsuka Mitsuaki Watanabe Sarah Coste Jean Baptiste Roullet Thongchan Phanouvang Eric Orwoll Shiela Orwoll David A McCarron 《Journal of applied physiology》2002,92(1):3-12
To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P < 0.001), elevated parathyroid hormone levels (P < 0.001), reduced calcitonin levels (P < 0.05), unchanged 1,25(OH)(2)D(3) levels, and elevated skull (P < 0.01) and reduced femur bone mineral density. Basal and thrombin-stimulated platelet free calcium (intracellular calcium concentration) were also reduced (P < 0.05). There was a tendency for indirect systolic BP to be reduced in conscious flight animals (P = 0.057). However, mean arterial pressure was elevated (P < 0.001) after anesthesia. Dietary calcium altered all aspects of calcium metabolism (P < 0.001), as well as BP (P < 0.001), but the only interaction with flight was a relatively greater increase in ionized calcium in flight animals fed low- compared with high-calcium diets (P < 0.05). The results indicate that 1) flight-induced disruptions of calcium metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing. 相似文献
44.
Mitsuaki Yamashita Masafumi Kaneko Harukuni Tokuda Katsumi Nishimura Yuko Kumeda Akira Iida 《Bioorganic & medicinal chemistry》2009,17(17):6286-6291
A series of naphthoquinones based on the naphtho[2,3-b]furan-4,9-dione skeleton such as (−)-5-hydroxy-2-(1′-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (1) and its positional isomer, (−)-8-hydroxy-2-(1′-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (2), which are secondary metabolites found in the inner bark of Tabebuia avellanedae, were stereoselectively synthesized and their biological activities were evaluated in conjunction with those of their corresponding enantiomers. Compound 1 exhibited potent antiproliferative effect against several human tumor cell lines, but its effect against some human normal cell lines was much lower than that of mitomycin. On the other hand, its enantiomer (R)-1 was less active toward the above tumor cell lines than 1. The antiproliferative effect of 2 against all tumor cell lines was significantly reduced. These results indicated the presence of the phenolic hydroxy group at C-5 is of great important for increasing antiproliferative effect. In addition, 1 also showed higher cancer chemopreventive activity than 2, while there were no significant differences between 1 and 2 in antimicrobial activity. Both compounds displayed modest antifungal and antibacterial activity (Gram-positive bacteria), whereas they were inactive against Gram-negative bacteria. 相似文献
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46.
Minamihata Tomoki Takano Katsura Nakamura Yoichi Seto Ryoya Moriyama Mitsuaki 《Neurochemical research》2022,47(9):2602-2616
Neurochemical Research - Mutations in alpha/beta-hydrolase domain containing (ABHD) 12 gene, which encodes lysophosphatidylserine (LysoPS) lipase, cause the neurodegenerative disease PHARC... 相似文献
47.
Onda K Shiraki R Ogiyama T Yokoyama K Momose K Katayama N Orita M Yamaguchi T Furutani M Hamada N Takeuchi M Okada M Ohta M Tsukamoto S 《Bioorganic & medicinal chemistry》2008,16(23):10001-10012
As a result of the various N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives with a hydroxy moiety synthesized in an effort to discover novel glycogen phosphorylase (GP) inhibitors, 5-chloro-N-(5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide (5b) was found to have potent inhibitory activity. The introduction of fluorine atoms both at a position adjacent to the hydroxy group and in the central benzene moiety lead to the optically active derivative 5-chloro-N-[(5R)-1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1H-indole-2-carboxamide (25e(alpha), which was the most potent compound in this series (IC(50)=0.020microM). This compound inhibited glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) value of 0.69microM, and showed oral hypoglycemic activity in diabetic db/db mice at 10mg/kg. Compound 25e(alpha) also had an excellent pharmacokinetic profile, with high oral bioavailability and a long plasma half-life, in male SD rats. The binding mode of 25e(alpha) to this molecule and the role of fluorine atoms in that binding were speculated in an enzyme docking study. 相似文献
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Ippei Sato Koichiro Morihira Hiroshi Inami Hirokazu Kubota Tatsuaki Morokata Keiko Suzuki Kazuki Ohno Yosuke Iura Aiko Nitta Takayuki Imaoka Toshiya Takahashi Makoto Takeuchi Mitsuaki Ohta Shin-ichi Tsukamoto 《Bioorganic & medicinal chemistry》2009,17(16):5989-6002
Our laboratory has identified several acrylamide derivatives with potent CCR3 inhibitory activity. In the present study, we evaluated the in vitro metabolic stability (CLint; mL/min/kg) of these compounds in human liver microsomes (HLMs), and assessed the relationship between their structures and CLint values. Among the compounds identified, N-{(3R)-1-[(6-fluoro-2-naphthyl)methyl]pyrrolidin-3-yl}-2-[1-(2-hydroxybenzoyl)piperidin-4-ylidene]acetamide (30j) was found to be a potent inhibitor (IC50 = 8.4 nM) with a high metabolic stability against HLMs. 相似文献
50.
Sawayama M Suzuki T Hashimoto H Kasai T Furutani M Miyata N Kunoh H Takada J 《Current microbiology》2011,63(2):173-180
Leptothrix species in aquatic environments produce uniquely shaped hollow microtubules composed of aquatic inorganic and bacterium-derived
organic hybrids. Our group termed this biologically derived iron oxide as “biogenous iron oxide (BIOX)”. The artificial synthesis
of most industrial iron oxides requires massive energy and is costly while BIOX from natural environments is energy and cost
effective. The BIOX microtubules could potentially be used as novel industrial functional resources for catalysts, adsorbents
and pigments, among others if effective and efficient applications are developed. For these purposes, a reproducible system
to regulate bacteria and their BIOX productivity must be established to supply a sufficient amount of BIOX upon industrial
demand. However, the bacterial species and the mechanism of BIOX microtubule formation are currently poorly understood. In
this study, a novel Leptothrix sp. strain designated OUMS1 was successfully isolated from ocherous deposits in groundwater by testing various culture media
and conditions. Morphological and physiological characters and elemental composition were compared with those of the known
strain L. cholodnii SP-6 and the differences between these two strains were shown. The successful isolation of OUMS1 led us to establish a basic
system to accumulate biological knowledge of Leptothrix and to promote the understanding of the mechanism of microtubule formation.
Additional geochemical studies of the OUMS1-related microstructures are expected provide an attractive approach to study the
broad industrial application of bacteria-derived iron oxides. 相似文献