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151.
Hideaki Yamaguchi Yumi Kidachi Katsuyoshi Kamiie Toshiro Noshita Hironori Umetsu 《Bioinformation》2012,8(23):1147-1153
Structural analysis of the high-mobility group protein B1 (HMGB1)-DNA complex and a docking simulation between
glycyrrhetinic acid (GA) and the HMGB1-DNA complex were performed with a software package the Molecular Operating
Environment (MOE). An HMGB1-DNA (PDB code: 2GZK) was selected for the 3D structure modeling of the HMGB1-DNA
complex. The Site Finder module of the MOE identified 16 possible ligand-binding sites in the modeled HMGB1-DNA complex.
The docking simulation revealed that GA possibly inhibits functions of HMGB1 interfering with Lys90, Arg91, Ser101, Tyr149, C230 and
C231 in the HMGB1-DNA complex. To the best of our knowledge, this is the first report of an HMGB1-DNA complex with GA, and
our data verify that the GA-HMGB1-DNA model can be utilized for application to target HMGB1 for the development of antitumor
drugs.
Abbreviations
ASE-Dock - alpha sphere and excluded volume-based ligand-protein docking, CNS - central nervous system, GA - glycyrrhetinic acid, GL - glycyrrhizin, HMGB1 - high-mobility group protein B1, LBS - ligand-biding site, MOE - Molecular Operating Environment, SRY - sex-determining region on the Y chromosome. 相似文献152.
The natural cytotoxic marine compound, jaspine B, is stereoselectively synthesized from D-xylose in 11 linear steps with a 23.9% overall yield. The key step in the synthesis involves an iodine-induced debenzylation of a primary alcohol and the subsequent 2,5-cyclization to fit the required configuration of jaspine B. A preliminary bioassay shows strong inhibition activities against human MDA231, Hela, and CNE cell lines, indicating potential usage in various cancer treatments. 相似文献
153.
Three ruthenium polypyridyl compounds of structural formula [Ru(apy)(tpy)Ln−](ClO4)(2−n) (apy = 2,2′-azobispyridine; tpy = 2,2′:6′,2″-terpyridine; L = Cl, H2O, CH3CN) (1a-c) were synthesized and crystallized. These complexes were fully characterized by means of 1D and 2D 1H NMR spectroscopy, as well as mass spectrometry and elemental analysis. Although in theory two isomers are possible, i.e. the one in which the central N atom in tpy is trans to the azo N in apy and the one in which the former is trans to the pyridine N in apy, in all cases only the latter was observed. The molecular structures of the compounds were elucidated by single-crystal X-ray diffraction. 相似文献
154.
Yi Liang Lei Feng Xin Tong De Feng Li Zi Jian Tang Shuai Jiang Da Cheng Wang Hui Sun 《Biochemical and biophysical research communications》2009,386(3):437-602
Agrocybe aegerita lectin (AAL) was identified previously in our group as a novel galectin from medicinal fungi Agrocybe aegerita, and has been shown to effectively induce cancer cell cycle arrest and apoptosis in vitro and tumor regression in vivo. Here, AAL was observed to translocate into the HeLa cell nucleus and induce cell apoptosis when it was predominantly in the nucleus. The N-terminus and C-terminus of AAL were required for nuclear localization. Site mutated proteins were generated based on AAL structure. Dimer interface mutant I25G, carbohydrate recognition domain (CRD) mutant R63H, and loop region mutant L33A could not enter the nucleus and lost the ability to induce apoptosis. CRD mutant H59Q and loop region mutant I144G maintained nuclear localization activity, and H59Q retained residual bioability but I144G had no activity, indicating that nuclear localization is important but not sufficient for AAL to become apoptotically active. Our findings provide a novel antitumor mechanism of fungal galectin. 相似文献
155.
Shi Zeng Fei-fei Nie Qing-Long Guo 《Biochemical and biophysical research communications》2009,385(4):551-556
LYG-202 is a newly synthesized flavonoid with a piperazine substitution. We investigated the antitumor effect of LYG-202 in vivo and in vitro. We show that, LYG-202 significantly decreases tumor growth in mice inoculated with S180 sarcoma cells, compared with the control group. Meanwhile, the viabilities of various kinds of tumor cells were inhibited by LYG-202 with IC50 values in the range of 4.80 to 27.70 μM. Then apoptosis induced by LYG-202 in HepG2 cells was characterized by DAPI staining and Annexin V/PI double staining and degradation of PARP was observed. Activation of the caspase cascade for both the extrinsic and intrinsic pathways was demonstrated, including caspase-8, -9, and -3. The results also showed that the expression of Bcl-2 protein decreased whereas that of Bax protein increased, leading to an increase of the Bax/Bcl-2 ratio. Our results demonstrated that LYG-202 exhibited strong antitumor effect in vivo and in vitro, involving with apoptosis induction. 相似文献
156.
Two kinds of xyloglucan derivatives (xyloglucan selenious ester and sulfated xyloglucan) were prepared and evaluated on antioxidant activity and antitumor activity. Compared with xyloglucan, xyloglucan derivatives have new bioactivity against oxidative damage and tumor. Furthermore, xyloglucan selenious ester is more potent than sulfated xyloglucan at antioxidant activity and antitumor activity in vitro. The current data suggest for the first time that selenition of xyloglucan significantly increases its bioactivity and the chemical modification of polysaccharide may allow the preparation of derivatives with new properties and a variety of applications. 相似文献
157.
旨在探讨金黄色葡萄球菌肠毒素A(SEA)在KM鼠体内的抑瘤效果.建立H22荷瘤小鼠模型,将20只小鼠随机分为对照组(生理盐水)、低剂量组(15 μg/ml)、中剂量组(25 μg/ml)和高剂量组(50 μg/ml),观察肿瘤生长趋势,计算抑瘤率,通过ELISA检测IL-2的含量.结果显示,给药组肿瘤生长趋势均较对照组缓慢;对照组、低剂量组、中剂量组、高剂量组的抑瘤率分别为0,28.9%,34.0%,51.0%(P<0.05);血清中IL-2含量分别为58.9 pg/ml、83.6 pg/ml、91.8 pg/ml、118.1 pg/ml.金黄色葡萄球菌肠毒素A(SEA)可抑制H22肿瘤的生长,并上调IL-2的分泌. 相似文献
158.
茯苓在药物化学、药理学、临床应用等方面有很高的使用价值。本文主要论述了茯苓药用的主要化学成分,在抗肿瘤和增强免疫力方面的作用,并对茯苓的前景进行了展望,为茯苓的进一步开发提供依据。 相似文献
159.
The self-complementary oligonucleotide CGCATATATGCG was used as a model to establish the binding interactions of antitumor molybdenocene dichloride and DNA. The free dodecamer was first characterized using 1H, NOESY, and DQF-COSY NMR experiments, which enable to pinpoint the guanines and adenines as well as the cytosines and thymines signals in the aromatic region. Molybdenocene dichloride was characterized in saline and buffer solutions as function of pH by 1H NMR spectroscopy. In 10 mM NaCl/D2O solution at pH of 6.5 and above, Cp2Mo(OD)(D2O)+ is in equilibrium with its dimeric species, [Cp2Mo(μ-OH)2MoCp2]2+. In 25 mM Tris/4 mM NaCl/D2O at physiological pH, a new stable species is formed, coordinated by the buffer, Tris(hydroxymethyl)aminomethane. The interactions of molybdenocene dichloride species with CGCATATATGCG were studied at different pH. At pH 6.5, in 4 mM NaCl/D2O solution, 1H NMR spectra of CGCATATATGCG exhibit downfield shifts in the signals associated mainly to adenines and guanines, upon addition of molybdenocene dichloride. At pH 7.4, in 25 mM Tris/4 mM NaCl/D2O, molybdenocene species causes broadening and small downfield shifts to the purines and pyrimidine signals, suggesting that molybdenocene dichloride can get engaged in binding interactions with the oligonucleotide in a weak manner. 31P NMR spectra of these interactions at pH 7.4 showed no changes associated to Mo(IV)-OP coordination, indicating that molybdenocene–oligonucleotide binding interactions are centered, most likely, on the bases. Cyclic voltammetry titration showed a 4.9% of molybdenocene–oligonucleotide interaction. This implicates that possible binding interactions with DNA are weak. 相似文献
160.
Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular modeling study of some new 4(3H)-quinazolinone analogs 总被引:1,自引:0,他引:1
Al-Rashood ST Aboldahab IA Nagi MN Abouzeid LA Abdel-Aziz AA Abdel-Hamide SG Youssef KM Al-Obaid AM El-Subbagh HI 《Bioorganic & medicinal chemistry》2006,14(24):8608-8621
In order to produce potent new leads for anticancer drugs, a new series of quinazoline analogs was designed to resemble methotrexate (MTX, 1) structure features and fitted with functional groups believed to enhance inhibition of mammalian DHFR activity. Molecular modeling studies were used to assess the fit of these compounds within the active site of human DHFR. The synthesized compounds were evaluated for their ability to inhibit mammalian DHFR in vitro and for their antitumor activity in a standard in vitro tissue culture assay panel. Compounds 28, 30, and 31 were the most active DHFR inhibitors with IC50 values of 0.5, 0.4, and 0.4 μM, respectively. The most active antitumor agents in this study were compounds 19, 31, 41, and 47 with median growth inhibitory concentrations (GI50) of 20.1, 23.5, 26.7, and 9.1 μM, respectively. Of this series of compounds, only compound 31 combined antitumor potency with potent DHFR inhibition; the other active antitumor compounds (19, 41, and 47) all had DHFR IC50 values above 15 μM, suggesting that they might exert their antitumor potency through some other mode of action. Alternatively, the compounds could differ significantly in uptake or concentration within mammalian cells. 相似文献