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Being able to carry zidovudine (AZT) at known concentrations into CD4+/CD38+ and CD14+ cells permits:
Further studies are necessary in order to:
相似文献
| - to reduce the drug dosage and to increase the interval for administration (until 1 dose I.V. every week); |
| - to modulate the drug concentration into the CD4+/CD38 an CD14+ cells in relation to the in vitro determined HIV sensitiveness; |
| - to eliminate haematological, medullary and general toxicity; |
| - to be able to treat severely hill patients. |
| - To find out the better phase to start the therapy; |
| - To use several drugs with different mechanisms of action in order to slow down as much as possible the presence of resistant viral strains. |
| - As for other drugs which are beginning to be used with artificial vehicles, futher studies are required to improve the selectivity and safety of LIPOAZT for the target cells including macrophages. |
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Piro MC Militello V Leone M Gryczynski Z Smith SV Brinigar WS Cupane A Friedman FK Fronticelli C 《Biochemistry》2001,40(39):11841-11850
The protein folding process of heme proteins entails generation of not only a correct global polypeptide structure, but also a correct, functionally competent heme environment. We employed a variety of spectroscopic approaches to probe the structure and dynamics of the heme pocket of a recombinant sperm whale myoglobin. The conformational characteristics were examined by circular dichroism, time-resolved fluorescence spectroscopy, FTIR spectroscopy, and optical absorption spectroscopy in the temperature range 300-20 K. Each of these spectroscopic probes detected modifications confined exclusively to the heme pocket of the expressed myoglobin relative to the native protein. The functional properties were examined by measuring the kinetics of CO binding after flash-photolysis. The kinetics of the expressed myoglobin were more heterogeneous than those of the native protein. Mild acid exposure of the ferric derivative of the recombinant protein resulted in a protein with "nativelike" spectroscopic properties and homogeneous CO binding kinetics. The heme pocket modifications observed in this recombinant myoglobin do not derive from inverted heme. In contrast, when native apomyoglobin is reconstituted with the heme in vitro, the heme pocket disorder could be attributed exclusively to 180 degrees rotation of the bound heme [La Mar, G. N., Toi, H., and Krishnamoorthi, R. (1984) J. Am. Chem. Soc. 106, 6395-6401; Light, W. R., Rohlfs, R. J., Palmer, G., and Olson, J. S. (1987) J. Biol. Chem. 262, 46-52]. We conclude that exposure to low pH decreases the affinity of globin for the heme and allows an extended conformational sampling or "soft refolding" to a nativelike conformation. 相似文献
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Federica Sinibaldi Barry D. Howes Maria Cristina Piro Fabio Polticelli Cecilia Bombelli Tommaso Ferri Massimo Coletta Giulietta Smulevich Roberto Santucci 《Journal of biological inorganic chemistry》2010,15(5):689-700
Two models have been proposed to explain the interaction of cytochrome c with cardiolipin (CL) vesicles. In one case, an acyl chain of the phospholipid accommodates into a hydrophobic channel of
the protein located close the Asn52 residue, whereas the alternative model considers the insertion of the acyl chain in the
region of the Met80-containing loop. In an attempt to clarify which proposal offers a more appropriate explanation of cytochrome
c–CL binding, we have undertaken a spectroscopic and kinetic study of the wild type and the Asn52Ile mutant of iso-1-cytochrome
c from yeast to investigate the interaction of cytochrome c with CL vesicles, considered here a model for the CL-containing mitochondrial membrane. Replacement of Asn52, an invariant
residue located in a small helix segment of the protein, may provide data useful to gain novel information on which region
of cytochrome c is involved in the binding reaction with CL vesicles. In agreement with our recent results revealing that two distinct transitions
take place in the cytochrome c–CL binding reaction, data obtained here support a model in which two (instead of one, as considered so far) adjacent acyl
chains of the liposome are inserted, one at each of the hydrophobic sites, into the same cytochrome c molecule to form the cytochrome c–CL complex. 相似文献
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Ferrer EG López Tévez LL Baeza N Correa MJ Okulik N Lezama L Rojo T Castellano EE Piro OE Williams PA 《Journal of inorganic biochemistry》2007,101(5):741-749
Two Cu(II) complexes with cyanoguanidine (cnge) and o-phenanthroline, [Cu(o-phen)(2)(cnge)](NO(3))(2).2H(2)O (1) and [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)] (2), have been synthesized using different experimental techniques and characterized by elemental analyses, FTIR, diffuse and UV-vis spectra and EPR and magnetic moment measurements techniques. The crystal structures of both complexes were solved by X-ray diffraction methods. Complex (1) crystallizes in the monoclinic space group C2/c with a=12.621(5), b=31.968(3), c=15.39(1)A, beta=111.68(4) degrees, and Z=8 and complex (2) in the monoclinic space group P2(1)/n with a=10.245(1), b=13.923(2), c=12.391(2)A, beta=98.07(1) degrees, and Z=4. The environments of the copper(II) center are trigonal bipyramidal (TBP) for [Cu(o-phen)(2)(cnge)](2+) and an elongated octahedron for [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)]. Solution studies have been performed to determine the species distribution. The superoxide dismutase (SOD) activities of both complexes have also been tested in order to determine if these compounds mimic the enzymatic action of the enzyme SOD that protects cells against peroxide radicals. 相似文献
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Mori F Piro FR Della Rocca C Mesiti G Giampaoli S Silvestre G Lazzaro D 《Histology and histopathology》2007,22(1):61-77
In the evolution of colon rectal cancer (CRC) the imbalance between cell proliferation and apoptosis is considered one of the prominent causes of tumor induction and/or progression. In order to establish the role of anti apoptotic proteins in colon cancer development, we studied with immunohistochemical techniques the expression of Survivin in a mouse model of colon carcinogenesis induced by 1,2-dimethyl-hydrazine treatment. In this mouse model Survivin was over-expressed during tumor development, showing a distribution mimicking that described in the correspondent human malignancies. We also correlated Survivin distribution with COX-2 and beta-Catenin expression patterns. The co-localization of COX-2/beta-Catenin/Survivin in the same epithelial cells in tumor samples lends credence to possible in vivo regulatory effects of COX-2 and beta-Catenin on the intracellular Survivin levels in mouse and human colon cancer. 相似文献