全文获取类型
收费全文 | 128篇 |
免费 | 5篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2018年 | 4篇 |
2016年 | 2篇 |
2015年 | 4篇 |
2014年 | 3篇 |
2013年 | 9篇 |
2012年 | 11篇 |
2011年 | 8篇 |
2010年 | 1篇 |
2009年 | 6篇 |
2008年 | 4篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 9篇 |
2004年 | 3篇 |
2003年 | 3篇 |
2002年 | 1篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1975年 | 1篇 |
排序方式: 共有133条查询结果,搜索用时 15 毫秒
1.
Hiroki Otani Hiromasa Yamamoto Munenori Takaoka Masakiyo Sakaguchi Junichi Soh Masaru Jida Tsuyoshi Ueno Takafumi Kubo Hiroaki Asano Kazunori Tsukuda Katsuyuki Kiura Shinji Hatakeyama Eiji Kawahara Yoshio Naomoto Shinichiro Miyoshi Shinichi Toyooka 《PloS one》2015,10(6)
TAE226, a bis-anilino pyrimidine compound, has been developed as an inhibitor of focal adhesion kinase (FAK) and insulin-like growth factor-I receptor (IGF-IR). In this study, we investigated the effect of TAE226 on non-small-cell lung cancer (NSCLC), especially focusing on the EGFR mutational status. TAE226 was more effective against cells with mutant EGFR, including the T790M mutant, than against cells with wild-type one. TAE226 preferentially inhibited phospho-EGFR and its downstream signaling mediators in the cells with mutant EGFR than in those with wild-type one. Phosphorylation of FAK and IGF-IR was not inhibited at the concentration at which the proliferation of EGFR-mutant cells was inhibited. Results of the in vitro binding assay indicated significant differences in the affinity for TAE226 between the wild-type and L858R (or delE746_A750) mutant, and the reduced affinity of ATP to the L858R (or delE746_A750) mutant resulted in good responsiveness of the L858R (or delE746_A750) mutant cells to TAE226. Of interest, the L858R/T790M or delE746_A750/T790M mutant enhanced the binding affinity for TAE226 compared with the L858R or delE746_A750 mutant, resulting in the effectiveness of TAE226 against T790M mutant cells despite the T790M mutation restoring the ATP affinity for the mutant EGFR close to that for the wild-type. TAE226 also showed higher affinity of about 15-fold for the L858R/T790M mutant than for the wild-type one by kinetic interaction analysis. The anti-tumor effect against EGFR-mutant tumors including T790M mutation was confirmed in mouse models without any significant toxicity. In summary, we showed that TAE226 inhibited the activation of mutant EGFR and exhibited anti-proliferative activity against NSCLCs carrying EGFR mutations, including T790M mutation. 相似文献
2.
3.
Kana Tsukuda Masaki Mogi Jun Iwanami Li-Juan Min Fei Jing Kousei Oshima Masatsugu Horiuchi 《Biochemical and biophysical research communications》2011,(2):275
Angiotensin II type 1 (AT1) receptor blockers (ARBs) are known to prevent the onset of stroke and to attenuate neural damage. Additional beneficial effects of ARBs, independent of AT1 receptor blockade, have been highlighted. Irbesartan is reported to act as an antagonist of the monocyte chemoattractant protein-1 (MCP-1) receptor, C–C chemokine receptor 2 (CCR2), due to its molecular structure. We examined the possible synergistic effects of co-administration of irbesartan with propagermanium, a CCR2 antagonist, on ischemic brain damage. Administration of propagermanium decreased ischemic brain area after middle cerebral artery occlusion (MCAO). To study the possible synergistic effects of propagermanium with ARBs, we employed non-effective lower doses of irbesartan and losartan. Administration of irbesartan with propagermanium decreased the ischemic brain area more markedly compared with propagermanium alone, but co-administration of losartan did not. MCP-1 mRNA level was significantly increased on the ipsilateral side after MCAO, and administration of irbesartan with propagermanium decreased the MCP-1 level, whereas co-administration of losartan did not. Similar results were obtained for MCP-1 protein level. CCR2 mRNA expression was significantly elevated on the ipsilateral side; however, no significant difference was observed between each group. mRNA levels of other inflammatory cytokines such as TNF-α and IL-1β also significantly increased on the ipsilateral side, but the expression levels were not changed by each drug treatment. Taking these findings together, irbesartan exerts more beneficial effects on ischemic brain damage with an MCP-1 receptor blocker, at least due to its inhibitory effects on MCP-1/CCR2 signaling beyond AT1 receptor blockade. 相似文献
4.
Agnese Mancini Jesse Senko Ricardo Borquez-Reyes Juan Guzman Póo Jeffrey A. Seminoff Volker Koch 《Human ecology: an interdisciplinary journal》2011,39(6):743-756
Despite complete legal protection, improvements in infrastructure, and market conditions that provide easier access to other
protein sources, illegal poaching of sea turtles for consumption in Baja California Sur (BCS), Mexico remains a major threat
to their recovery. Few studies have focused on understanding the economic and social drivers behind this activity, which is
fundamental to determining best practices for discouraging it. From June 2007 to April 2008 we conducted eight in-depth, semi-structured
interviews with sea turtle poachers at five coastal communities in BCS to determine the drivers influencing them. The most
prevalent reasons for illegal poaching were direct economic benefits, lack of law enforcement and ease of escape from or bribery
of authorities, and strong family tradition. Our results suggest that to reduce illegal poaching it will be necessary to better
enforce existing environmental laws, reduce social acceptance of sea turtle hunting throughout the region, educate fishers
on the ecological importance of sea turtles, and show fishers direct economic benefits from non-consumptive use of sea turtles,
such as ecotourism. 相似文献
5.
Daisuke Sawada Tomoyuki Katayama Yuya Tsukuda Nozomi Saito Masashi Takano Hiroshi Saito Ken-ichiro Takagi Eiji Ochiai Seiichi Ishizuka Kazuya Takenouchi Atsushi Kittaka 《Bioorganic & medicinal chemistry letters》2009,19(18):5397-5400
We synthesized and isolated 2α-substituted analogs of 14-epi-previtamin D3 after thermal isomerization at 80 °C for the first time. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the 2α-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D3. 相似文献
6.
Seigen Tsukuda Masahito Sugiyama Yunosuke Harita Kazuo Nishimura 《Biogeochemistry》2006,77(1):117-138
Atmospheric bulk depositions of soluble reactive phosphorus (SRP), soluble unreactive phosphorus (SUP), particulate inorganic
phosphorus (PIP), particulate organic phosphorus (POP), total phosphorus (TP) and some other dissolved and particulate components
were monitored for 3 years in Ashiu, Central Japan. The mean bulk depositions of SRP, SUP, PIP, POP, TP, dissolved components
(Na, Mg, nss-Ca, K, V, Mo, nss-SO4) and particulate components (Al, Fe, Ti, Ca, Mg, Mn, Ba, Sr, Zn) were 175, 76, 136, 397, 783, 156,000, 10,900, 7450, 5470,
10.3, 1.52, 40,100, 13,200, 3590, 2630, 576, 624, 42.3, 30.2, 17.4, 8.2 μmol m−2 year−1, respectively. The value for TP deposition was in the lower range of previous literature. The low P deposition probably reflected
the method applied to reduce the contribution of local particles, including (1) placement of samplers off the ground surface,
(2) installation of multiple samplers, and (3) rejection of contaminated samples. Al data suggested that 15 ± 5% of TP was
brought by lithogenic dust from East Eurasia. Nss-SO4 and Mo data and air-mass backward trajectories suggested that 39 ± 4% of TP was derived from coal combustion in China. It
was speculated that the rest (47 ± 6%) of the TP deposition might be predominantly attributed to the contribution of local
biogenic particles. Net atmospheric TP input (lithogenic dust and fossil fuel combustion) was almost equal to the TP outflow
from Japanese forests on granitic soils. 相似文献
7.
Effect of Oxidation Rate and Fe(II) State on Microbial Nitrate-Dependent Fe(III) Mineral Formation 下载免费PDF全文
A nitrate-dependent Fe(II)-oxidizing bacterium was isolated and used to evaluate whether Fe(II) chemical form or oxidation rate had an effect on the mineralogy of biogenic Fe(III) (hydr)oxides resulting from nitrate-dependent Fe(II) oxidation. The isolate (designated FW33AN) had 99% 16S rRNA sequence similarity to Klebsiella oxytoca. FW33AN produced Fe(III) (hydr)oxides by oxidation of soluble Fe(II) [Fe(II)sol] or FeS under nitrate-reducing conditions. Based on X-ray diffraction (XRD) analysis, Fe(III) (hydr)oxide produced by oxidation of FeS was shown to be amorphous, while oxidation of Fe(II)sol yielded goethite. The rate of Fe(II) oxidation was then manipulated by incubating various cell concentrations of FW33AN with Fe(II)sol and nitrate. Characterization of products revealed that as Fe(II) oxidation rates slowed, a stronger goethite signal was observed by XRD and a larger proportion of Fe(III) was in the crystalline fraction. Since the mineralogy of Fe(III) (hydr)oxides may control the extent of subsequent Fe(III) reduction, the variables we identify here may have an effect on the biogeochemical cycling of Fe in anoxic ecosystems. 相似文献
8.
Abstract The research conducted here presents a syntaxonomical revision of the montane mesophilous meadows of the Polygono bistortae-Trisetion flavescentis alliance in central Europe – the Slovak part of the western and eastern Carpathians. These typical semi-natural grasslands occur mainly as small islands over the calcareous bedrocks. Associations of this alliance have tight relationships to the Arrhenatherion, Mesobromion and Nardo-Agrostion alliances. Formal definitions based on combination of the species groups were used regarding the diversity and geographical range of the Polygono bistortae-Trisetion flavescentis alliance. Following the formal definitions from the eight associations reported previously for Slovakia, only four of them can be placed within the Polygono bistortae-Trisetion flavescentis: Campanulo glomeratae-Geranietum sylvatici, Geranio sylvatici-Trisetetum, Crepido mollis-Agrostietum capillaries and Geranio-Alchemilletum crinitae. A comparison of traditional and formalized classification, and the advantages/disadvantages of the formalized classification are discussed. 相似文献
9.
Masashi Iwamoto Koichi Watashi Senko Tsukuda Hussein Hassan Aly Masayoshi Fukasawa Akira Fujimoto Ryosuke Suzuki Hideki Aizaki Takayoshi Ito Osamu Koiwai Hiroyuki Kusuhara Takaji Wakita 《Biochemical and biophysical research communications》2014
Hepatitis B virus (HBV) entry has been analyzed using infection-susceptible cells, including primary human hepatocytes, primary tupaia hepatocytes, and HepaRG cells. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) membrane transporter was reported as an HBV entry receptor. In this study, we established a strain of HepG2 cells engineered to overexpress the human NTCP gene (HepG2-hNTCP-C4 cells). HepG2-hNTCP-C4 cells were shown to be susceptible to infection by blood–borne and cell culture-derived HBV. HBV infection was facilitated by pretreating cells with 3% dimethyl sulfoxide permitting nearly 50% of the cells to be infected with HBV. Knockdown analysis suggested that HBV infection of HepG2-hNTCP-C4 cells was mediated by NTCP. HBV infection was blocked by an anti-HBV surface protein neutralizing antibody, by compounds known to inhibit NTCP transporter activity, and by cyclosporin A and its derivatives. The infection assay suggested that cyclosporin B was a more potent inhibitor of HBV entry than was cyclosporin A. Further chemical screening identified oxysterols, oxidized derivatives of cholesterol, as inhibitors of HBV infection. Thus, the HepG2-hNTCP-C4 cell line established in this study is a useful tool for the identification of inhibitors of HBV infection as well as for the analysis of the molecular mechanisms of HBV infection. 相似文献
10.
The dose dependent effect of ipriflavone (7-isopropoxy-isoflavone) on the femoral bone in streptozotocin-induced diabetic rats was studied by microdensitometric analysis. Diabetic rats showed severe hyperglycemia, glucosuria, hypoinsulinemia, associated with increased urinary calcium and hydroxyproline. Microdensitometric analysis revealed decreases in femoral length, bone width, and bone density. The dietary administration of ipriflavone (about 270 mg/kg/day) to the diabetic rats for 6 weeks prevented reduction of the cortical thickness index in the diaphysis and depletion of bone density in the distal metaphysis, and also reduced the inner diameter of the diaphysis; diabetic state was not improved. A simple correlation and linear regression analysis revealed that ipriflavone also significantly reduced the inner diameter in the diaphysis at a dose of 90 mg/kg/day, but not at one of 25 mg/kg/day. These results suggest that ipriflavone suppresses the depletion of the femoral bone through inhibition of bone resorption in a dose dependent fashion; its minimum effective dose is 90 mg/kg/day in experimental diabetes. 相似文献