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41.
Selective Ablation of β‐Galactosidase‐Expressing Cells with a Rationally Designed Activatable Photosensitizer
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Dr. Yuki Ichikawa Dr. Mako Kamiya Dr. Fumiaki Obata Prof. Masayuki Miura Dr. Takuya Terai Dr. Toru Komatsu Dr. Tasuku Ueno Dr. Kenjiro Hanaoka Prof. Tetsuo Nagano Prof. Yasuteru Urano 《Angewandte Chemie (International ed. in English)》2014,53(26):6772-6775
We have developed an activatable photosensitizer capable of specifically inducing the death of β‐galactosidase‐expressing cells in response to photoirradiation. By using a selenium‐substituted rhodol scaffold bearing β‐galactoside as a targeting substituent, we designed and synthesized HMDESeR‐βGal, which has a non‐phototoxic spirocyclic structure owing to the presence of the galactoside moiety. However, β‐galactosidase efficiently converted HMDESeR‐βGal into phototoxic HMDESeR, which exists predominantly in the open xanthene form. This structural change resulted in drastic recovery of visible‐wavelength absorption and the ability to generate singlet oxygen (1O2). When HMDESeR‐βGal was applied to larval Drosophila melanogaster wing disks, which express β‐galactosidase only in the posterior region, photoirradiation induced cell death in the β‐galactosidase‐expressing region with high specificity. 相似文献
42.
Shigeyuki Hanaoka Eiko Nagasawa Koji Nomura Masaru Yamazawa Mutsuo Ishizaki 《应用有机金属化学》2005,19(2):265-275
To elucidate the current extent of pollution of the environment with diphenylarsine chloride (DA, Clark I) and diphenylarsine cyanide (DC, Clark II), we have developed analytical procedures using gas and liquid chromatography and employed them to analyze water and soil samples. DA, DC, and their degradation products were extracted with water or organic solvents. Derivatization with n‐propanethiol was adopted to achieve higher analytical reproducibility. DA and DC were unstable and decomposed into bis(diphenylarsine)oxide (BDPAO) in water, but only negligibly into diphenylarsinic acid (DPAA) during the 30 days of a stability test. Diphenylarsenic compounds afforded the same product by this derivatization, but their reaction rates varied depending on the starting materials. DPAA had to be treated under acidic conditions at 60 °C to achieve the desired conversion efficiency. Recovery of the thiol derivatives of the diphenylarsenic compounds tested was almost quantitative from water, but only about 50% from soil, reflecting the low extraction efficiency. We applied the method to the analysis of organoarsenic compounds sampled from the water of the drinking well in Kamisu‐cho, Ibaraki Prefecture, where the water was thought to have had deleterious effects on the inhabitants. The high level of DPAA was identified as the causative agent. Our analyses of soil samples from Samukawa‐cho and Hiratsuka City, Kanagawa Prefecture, where a naval arsenal had previously stood, succeeded in identifying intact DA, BDPAO and triphenylarsine, diphenylarsenic thiol‐derivatives, as well as other substances (mustard gas, lewisite). The true magnitude of contamination became evident after these measurements. Copyright © 2005 John Wiley & Sons, Ltd. 相似文献
43.
A Single Fluorescent Probe to Visualize Hydrogen Sulfide and Hydrogen Polysulfides with Different Fluorescence Signals
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Dr. Wei Chen Armando Pacheco Yoko Takano Jacob J. Day Prof. Dr. Kenjiro Hanaoka Prof. Dr. Ming Xian 《Angewandte Chemie (International ed. in English)》2016,55(34):9993-9996
Hydrogen sulfide (H2S) and hydrogen polysulfides (H2Sn, n>1) are endogenous regulators of many physiological processes. In order to better understand the symbiotic relationship and cellular cross‐talk between H2S and H2Sn, it is highly desirable to develop single fluorescent probes which enable dual‐channel discrimination between H2S and H2Sn. Herein, we report the rational design, synthesis, and evaluation of the first dual‐detection fluorescent probe DDP‐1 that can visualize H2S and H2Sn with different fluorescence signals. The probe showed high selectivity and sensitivity to H2S and H2Sn in aqueous media and in cells. 相似文献
44.
Fujikawa Y Urano Y Komatsu T Hanaoka K Kojima H Terai T Inoue H Nagano T 《Journal of the American Chemical Society》2008,130(44):14533-14543
Here we report the development of fluorogenic substrates for glutathione S-transferase (GST), a multigene-family enzyme mainly involved in detoxification of endogenous and exogenous compounds, including drug metabolism. GST is often overexpressed in a variety of malignancies and is involved in the development of resistance to various anticancer drugs. Despite the medical significance of this enzyme, no practical fluorogenic substrates for fluorescence imaging of GST activity or for high-throughput screening of GST inhibitors are yet available. So, we set out to develop new fluorogenic substrates for GST. In preliminary studies, we found that 3,4-dinitrobenzanilide (NNBA) is a specific substrate for GST and established the mechanisms of its glutathionylation and denitration. Using these results as a basis for off/on control of fluorescence, we designed and synthesized new fluorogenic substrates, DNAFs, and a cell membrane-permeable variant, DNAT-Me. These fluorogenic substrates provide a dramatic fluorescence increase upon GST-catalyzed glutathionylation and have excellent kinetic parameters for the present purpose. We were able to detect nuclear localization of GSH/GST activity in HuCCT1 cell lines with the use of DNAT-Me. These results indicate that the newly developed fluorogenic substrates should be useful not only for high-throughput GST-inhibitor screening but also for studies on the mechanisms of drug resistance in cancer cells. 相似文献
45.
Kumagai M Imai Y Nakamura T Yamasaki Y Sekino M Ueno S Hanaoka K Kikuchi K Nagano T Kaneko E Shimokado K Kataoka K 《Colloids and surfaces. B, Biointerfaces》2007,56(1-2):174-181
PEG-coated β-FeOOH nanoparticles were prepared through electrostatic complex formation of iron oxide nanoparticles with poly(ethylene glycol)-poly(aspartic acid) block copolymer [PEG-P(Asp)] in distilled water. By dynamic light scattering (DLS) measurement, the nanopaticle size was determined to be 70 nm with narrow distribution. The FT-IR and zeta potential experimental results proved that PEG-PAsp molecules bound to the surface of the iron oxide nanoparticles via the coordination between the carboxylic acid residues in the PAsp segment of the block copolymer and the surface Fe of the β-FeOOH nanoparticles. The PEG-coated nanoparticles revealed excellent solubility and stability in aqueous solution as well as in physiological saline. In vivo MRI experiments on tumor-bearing mice demonstrated that the PEG-coated nanoparticles prepared by the current approach achieved an appreciable accumulation into solid tumor, suggesting their potential utility as tumor-selective MRI contrast agents. 相似文献
46.
Hanaoka K Kikuchi K Kobayashi S Nagano T 《Journal of the American Chemical Society》2007,129(44):13502-13509
Superior fluorescence imaging methods are needed for detailed studies on biological phenomena, and one approach that permits precise analyses is time-resolved fluorescence measurement, which offers a high signal-to-noise ratio. Herein, we describe a new fluorescence imaging system to visualize biomolecules within living biological samples by means of time-resolved, long-lived luminescence microscopy (TRLLM). In TRLLM, short-lived background fluorescence and scattered light are gated out, allowing the long-lived luminescence to be selectively imaged. Usual time-resolved fluorescence microscopy provides fluorescence images with nanosecond resolution and has been used to image interactions between proteins, protein phosphorylation, the local pH, the refractive index, ion or oxygen concentrations, etc. Luminescent lanthanide complexes (especially europium and terbium trivalent ions (Eu3+ and Tb3+)), in contrast, have long luminescence lifetimes on the order of milliseconds. We have designed and synthesized new luminescent Eu3+ complexes for TRLLM and also developed a new TRLLM system using a conventional fluorescence microscope with an image intensifier unit for gated signal acquisition and a xenon flash lamp as the excitation source. When the newly developed luminescent Eu3+ complexes were applied to living cells, clear fluorescence images were acquired with the TRLLM system, and short-lived fluorescence was completely excluded. By using Eu3+ and Tb3+ luminescent complexes in combination, time-resolved dual-color imaging was also possible. Furthermore, we monitored changes of intracellular ionic zinc (Zn2+) concentration by using a Zn2+-selective luminescent Eu3+ chemosensor, [Eu-7]. This new imaging technique should facilitate investigations of biological functions with fluorescence microscopy, complementing other fluorescence imaging methodologies. 相似文献
47.
Koide Y Urano Y Hanaoka K Piao W Kusakabe M Saito N Terai T Okabe T Nagano T 《Journal of the American Chemical Society》2012,134(11):5029-5031
We have developed a series of novel near-infrared (NIR) wavelength-excitable fluorescent dyes, SiR-NIRs, by modifying the Si-rhodamine scaffold to obtain emission in the range suitable for in vivo imaging. Among them, SiR680 and SiR700 showed sufficiently high quantum efficiency in aqueous media. Both antibody-bound and free dye exhibited high tolerance to photobleaching in aqueous solution. Subcutaneous xenograft tumors were successfully visualized in a mouse tumor model using SiR700-labeled anti-tenascin-C (TN-C) antibody, SiR700-RCB1. SiR-NIRs are expected to be useful as labeling agents for in vivo imaging studies including multicolor imaging, and also as scaffolds for NIR fluorescence probes. 相似文献
48.
Production of no-carrier-added 64Cu and applications to molecular imaging by PET and PETIS as a biomedical tracer 总被引:1,自引:0,他引:1
S. Watanabe Y. Iida N. Suzui T. Katabuchi S. Ishii N. Kawachi H. Hanaoka S. Watanabe S. Matsuhashi K. Endo N. S. Ishioka 《Journal of Radioanalytical and Nuclear Chemistry》2009,280(1):199-205
Copper-64 was produced by the 64Ni(p, n)64Cu reaction using enriched 64NiO target. We investigated and compared the production yield of 64Cu for proton beams of various energies by using a thick target. Enriched 64Ni was recovered with high yield by simple procedures. Imaging studies using positron emission tomography (PET) and positron
emitting tracer imaging system (PETIS) were performed. We obtained clear images in PET and PETIS studies. The results of this
study indicate that 64Cu can be utilized as a biomedical tracer for the molecular imaging both in animals and plants. 相似文献
49.
Noriaki Miura Yuuki Noto Shuusuke Kato Fumihito Yokoyama Susumu Kuwamura Naoshi Baba Yoichiro Hanaoka Shin’ichi Nagata Satoru Ueno Reizaburou Kitai Kiyoshi Ichimoto Hideki Takami 《Optical Review》2009,16(5):558-561
A solar adaptive optics system has been improved by using a high-speed electromagnetic deformable mirror and adopting a modified sum-of-absolute-differences algorithm in wavefront sensing. Results of laboratory experiments clearly show that the use of the mirror raises the temporal performance of the system. In solar observations, wavefront compensation using solar granules as a target is realized. 相似文献
50.
Ken'ichi Hanaoka Walter Goessler Hirokazu Ohno Kurt J. Irgolic Toshikazu Kaise 《应用有机金属化学》2001,15(1):61-66
Arsenobetaine, an organo‐arsenic compound known to be non‐toxic, occurs ubiquitously in marine animals. To elucidate the food hygiene safety of the degradation products of arsenobetaine formed on cooking, arsenicals generated by roasting the muscles of the starspotted shark Mustelus manazo and of the red crayfish Panulirus longipes femoristriga were investigated. As a result, both muscle types were found to contain the tetramethylarsonium ion, which is reported to show a higher acute toxicity than dimethylarsinic acid (cacodylic acid) or methanearsonic acid. As a minor compound, arsenate was also detected in the muscle of M. manazo. Copyright © 2001 John Wiley & Sons, Ltd. 相似文献