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161.
Interaction of [3 H](–)-SKF-10,047 with Brain σ Receptors: Characterization and Autoradiographic Visualization 总被引:2,自引:0,他引:2
Stephen R. Zukin† Ann Tempel† Eliot L. Gardner† R. Suzanne Zukin† 《Journal of neurochemistry》1986,46(4):1032-1041
The sigma opiates differ from other opiates in their stimulatory and psychotomimetic actions. The sigma opiate [3H](-)-SKF-10,047 has been used to characterize sigma receptors in rat nervous tissue. Binding of [3H](-)-SKF-10,047 to rat brain membranes was of high affinity, saturable, and reversible. Scatchard analysis revealed the apparent interaction of this drug with two distinct binding sites characterized by affinities of 0.03 and 75 nM (5 mM Tris-HCl buffer, pH 7.4, at 4 degrees C). Competition analyses involving rank order determinations for a series of opiates and other drugs indicate that the high-affinity binding site is the mu opiate receptor. The lower-affinity site (revealed after suppression of mu and delta receptor binding) has been identified as the sigma opiate/phencyclidine receptor. In vitro autoradiography has been used to visualize neuroanatomical patterns of receptors labeled using [3H](-)-SKF-10,047 in the presence of normorphine and [D-Ala2,D-Leu5]enkephalin to block mu and delta interactions, respectively. Labeling patterns differ markedly from those for mu, delta, or kappa receptors. The highest densities (determined by quantitative autoradiography) are found in the medial portion of the nucleus accumbens, amygdaloid nucleus, hippocampal formation, central gray, locus coeruleus, and the parabrachial nuclei. Receptors in these structures could account for the stimulatory, mood-altering, and analgesic properties of the sigma opiates. Although not the most selective sigma opiate ligand, [3H](-)-SKF-10,047 binds to sigma opiate receptors in brain, and this interaction can be readily distinguished from its interactions with other classes of brain opiate receptors. 相似文献
162.
Protein factors which regulate cell motility 总被引:11,自引:0,他引:11
Eliot M. Rosen Itzhak D. Goldberg 《In vitro cellular & developmental biology. Plant》1989,25(12):1079-1087
Summary Cell motility (i.e., movement) is an essential component of normal development, inflammation, tissue repair, angiogenesis,
and tumor invasion. Various molecules can affect the motility and positioning of mammalian cells, including peptide growth
factors, (e.g., EGF, PDGF, TGF-beta), substrate-adhesion molecules (e.g., fibronectin, laminin), cell adhesion molecules (CAMs),
and metalloproteinases. Recent studies have demonstrated a group of motility-stimulating proteins which do not appear to fit
into any of the above categories. Examples include: 1)scatter factor (SF), a mesenchymal cell-derived protein which causes contiguous sheets of epithelium to separate into individual cells and stimulates
the migration of epithelial as well as vascular endothelial cells; 2)autocrine motility factor (AMF), a tumor cell-derived protein which stimulates migration of the producer cells; and 3)migration-stimulating factor (MSF), a protein produced by fetal and cancer patient fibroblasts which stimulates penetration of three-dimensional collagen gels
by non-producing adult fibroblasts. SF, AMF, and MSF are soluble and heat labile proteins with Mr of 77, 55, and 70 kd by
SDS-PAGE, respectively, and may be members of a new class of cell-specific regulators of motility. Their physiologic functions
have not been established, but available data suggest that they may be involved in fetal development and/or tissue repair. 相似文献
163.
Eliot M. Rosen Itzhak D. Goldberg Barry M. Kacinski Thomas Buckholz David W. Vinter 《In vitro cellular & developmental biology. Plant》1989,25(2):163-173
Summary We report that culture bovine calf aorta and human adult iliac artery smooth muscle cells release a soluble factor which causes
spreading and separation of cells in normally tight, cohesive epithelial colonies, similar to the morphologic changes induced
by the fibroblast-derived scatter factor (SF). Smooth muscle-derived SF was heat sensitive, trypsin labile, and nondialyzable,
consistent with a protein (or proteins). Its effects on epithelium were not mimicked by a variety of proteolytic enzymes,
growth factors, or hormones, and were not blocked by antiproteases or by antibodies to fibronectin and basic fibroblast growth
factor. Epithelial cell proliferation was unaffected or only mildly stimulated by partially purified SF at concentrations
that produced cell scattering. Both smooth muscle-and MRC5 human embryo fibroblast-derived SFs could be partially purified
with similar elution patterns on a number of different chromatographic columns, including DEAE-agarose, heparin-sepharose,
Bio-Rex 70, concanavalin A-sepharose, and MonoQ. SF from both sources bound tightly to heparin-sepharose, requiring 1.3 to
1.4M NaCl for elution. The morphologically obvious cell scattering effect was markedly inhibited by soluble heparin at concentrations
down to 5 μg/ml, and this inhibition was prevented by protamine. These data suggest that vascular smooth muscle cells produce
an epithelial cell scattering factor with properties similar to the fibroblast-produced factor, including a high affinity
for heparin. Such factors are potentially important because they may represent a new class of proteins that primarily regulate
cell mobility rather than growth and differentiation.
Supported by American Cancer Society grant ACS IN-31-28-5, an Argail L. and Anna G. Hull Cancer Research Award, and grants-in-aid
from the American Heart Association (#880981) and the American Lung Association of Connecticut. Dr. Goldberg was supported
by the LIJ-Harvard Research Consortium and the Finkelstein Foundation. 相似文献
164.
Birandra K. Sinha William M. Antholine B. Kalyanaraman Helen M. Eliot 《生物化学与生物物理学报:疾病的分子基础》1990,1096(1):81-83
The dihydroxy etoposide, a metabolite of the clinically active anticancer drug, VP-16, induced extensive DNA damage in the presence of copper ions. While superoxide dismutase was without any effect on the DNA damage, catalase and inhibitors of free hydroxyl radicals inhibited the DNA degradation, indicating that hydroxyl radicals were responsible for this drug-Cu-dependent DNA damage. 相似文献
165.
Loic Faye John S. Greenwood Eliot M. Herman Arnd Sturm Maarten J. Chrispeels 《Planta》1988,174(2):271-282
-Mannosidase (EC 3.2.1.24) is a vacuolar enzyme which occurs abundantly in the cotyledons of the jack-bean (Canavalia ensiformis (L.) DC). The mature enzyme is a tetramer with two polypeptides each of relative molecular mass (Mr) 66000 and Mr 44000. The enzyme has an interesting molecular structure because in its native form, it does not bind to concanavalin A (ConA) in spite of the presence of a high-mannose glycan. -Mannosidase is synthesized in the developing cotyledons of jack-beans at the same time as the abundant proteins canavalin and ConA. The enzyme is synthesized as a precursor which has an Mr of 110000 and is associated with the endoplasmic reticulum (ER). Antibodies against the deglycosylated subunits cross-react with the Mr-110000 precursor. Processing of the precursor to the constituent polypeptides occurs posttranslationally, probably in the protein bodies. Immunocytochemical evidence shows that -mannosidase is present in the ER and the Golgi complex of developing cells, and accumulates in the protein bodies.Labeling with [3H]glucosamine shows that after processing only the Mr-66000 polypeptide has glucosamine-containing glycans. The synthesis of these glycans is inhibited by tunicamycin, indicating that they are asparagine-linked oligosaccharides. Analysis of the glycans shows that there is a large glycan that is retained by ConA and a small glycan that is not retained by ConA. The large glycan is only partially sensitive to -mannosidase because of the presence of a terminal glucose residue. Cross-reaction of the large subunit with an antiserum directed against small, complex glycans of plant glycoproteins indicates that this polypeptide probably has a xylose-containing glycan. Pulse-chase experiments carried out in the presence of tunicamycin show that the presence of glycans is not required for transport of -mannosidase out of the ER-Golgi system.Abbreviations ConA
concanavalin A
- ER
endoplasmic reticulum
- H L
heavy, light subunit
- IgG
Immunoglobulin G
- Mr
relative molecular mass
- SDS-PAGE
sodium dodecylsulfate-polyacrylamide gel electrophoresis 相似文献
166.
We used a heterologous system (transgenic Nicotiana tabacum L.) to investigate the processing, assembly and targeting of phytohemagglutinin (PHA), the lectin of the common bean, Phaseolus vulgaris L. In the bean, this glycoprotein accumulates in the protein bodies of the storage parenchyma cells in the cotyledons, and each polypeptide has a high-mannose glycan attached to Asn12 and a complex glycan on Asn60. The gene for PHA-L, dlec2, with 1200 basepairs (bp) 5 upstream and 1600 bp 3 downstream from the coding sequence was introduced into tobacco using Agrobacterium-mediated transformation (T. Voelker et al., 1987, EMBO J. 6, 3571–3577). Examination of thin sections of tobacco seeds by immunocytochemistry with antibodies against PHA showed that PHA-L accumulated in the amorphous matrix of the protein bodies in the embryo and endosperm. This localization was confirmed using a non-aqueous method to isolate the protein bodies from mature tobacco seeds. The biochemical analysis of tobacco PHA indicated that the signal peptide had been correctly removed, and that the polypeptides formed 6.4 S oligomers; tobacco PHA had a high-mannose glycan at Asn12 and a complex glycan at Asn60. The presence of the complex glycan shows that transport to the protein bodies was mediated by the Golgi complex. At seed maturity, a substantial portion of the PHA-L remained associated with the endoplasmic reticulum and the Golgi complex, as indicated by fractionation experiments using aqueous media and the presence of two high-mannose glycans on some of the polypeptides. Taken together, these data show that insertion of the nascent PHA into the endoplasmic reticulum, signal peptide processing, glycosylation, assembly into oligomers, glycan modification in the Golgi, and targeting of the protein occur faithfully in this heterologous system, although transport may not be as efficient as in bean cotyledons.Abbreviations Asn
asparagine
- Endo H
endoglycosidase H
- HPLC
high-performance liquid chromatography
- IgG
immunoglobulin G
- Mr
relative molecular mass
- PAGE
polyacrylamide gel electrophoresis
- PHA
phytohemagglutinin
- SDS
sodium dodecylsulfate
- TFMS
trifluoromethanesulfonic acid 相似文献
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