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51.
Susann Richert Nancy B Wehr Earl R Stadtman Rodney L Levine 《Archives of biochemistry and biophysics》2002,397(2):430-432
The oxidative modification of proteins by reactive species, especially reactive oxygen species, is implicated in the etiology or progression of a panoply of disorders and diseases. For the most part, oxidatively modified proteins are not repaired and must be removed by proteolytic degradation. The level of these modified molecules can be quantitated by measurement of the protein carbonyl content, which has been shown to increase in a variety of diseases and processes, most notably during aging. However, these studies have required invasive techniques to obtain cells for analysis. We examined the possibility that desquamating skin cells (corneocytes) would also show an age-related increase in protein carbonyl content, thus providing a noninvasive method for assessing biological age. This was not the case, as we found no age-dependent relationship in the protein carbonyl content of skin cells from volunteers aged 20 to 79 years. 相似文献
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On isolated coronary arteries of cattle, nitroprusside-sodium, nitroglycerol, prenylamine, and verapamil were studied for their spasmolytic effects on a contracture induced by fluoride ions. With this contracture model, which is independent of extracellular calcium, nitroprosside-sodium and nitroglycerol showed strong spasmolytic action. Verapamil proved ineffective, and the effectiveness of prenylamine was strongly reduced. The results lend support to earlier findings suggesting that nitroglycerol and nitroprusside-sodium are endowed with a relaxation mechanism different from that of verapamil and analogously acting compounds. 相似文献
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Lena Jansson Jonas Ångström Michael Lebens Susann Teneberg 《Glycoconjugate journal》2010,27(1):171-179
A novel carbohydrate binding site recognizing blood group A and B determinants in a hybrid of cholera toxin and Escherichia coli heat-labile enterotoxin B-subunits (termed LCTBK) has previously been described, and also the native heat-labile enterotoxin bind to some extent to blood group A/B terminated
glycoconjugates. The blood group antigen binding site is located at the interface of the B-subunits. Interestingly, the same
area of the B-subunits has been proposed to be involved in binding of the heat-labile enterotoxin to lipopolysaccharides on
the bacterial cell surface. Binding of the toxin to lipopolysaccharides does not affect the GM1 binding capacity. The present
study aimed at characterizing the relationship between the blood group A/B antigen binding site and the lipopolysaccharide
binding site. However, no binding of the B-subunits to E. coli lipopolysaccharides in microtiter wells or on thin-layer chromatograms was obtained. Incubation with lipopolysaccharides
did not affect the binding of the B-subunits of heat-labile enterotoxin of human isolates to blood group A-carrying glycosphingolipids,
indicating that the blood group antigen site is not involved in LPS binding. However, the saccharide competition experiments
showed that GM1 binding reduced the affinity for blood group A determinants and vice versa, suggesting that a concurrent occupancy of the two binding sites does not occur. The latter finding is related to a connection
between the blood group antigen binding site and the GM1 binding site through residues interacting with both ligands. 相似文献
57.
D?rthe M Katschinski Lu Le Susann G Schindler Tim Thomas Anne K Voss Roland H Wenger 《Cellular physiology and biochemistry》2004,14(4-6):351-360
Hypoxia-inducible factor (HIF) alpha subunits are induced under hypoxic conditions, when limited oxygen supply prevents prolyl hydroxylation-dependent binding of the ubiquitin ligase pVHL and subsequent proteasomal degradation. A short normoxic half-life of HIF-alpha and a very rapid hypoxic protein stabilization are crucial to the cellular adaptation to changing oxygen supply. However, the molecular requirements for the unusually rapid mechanisms of protein synthesis, folding and nuclear translocation are not well understood. We and others previously found that the chaperone heat-shock protein 90 (HSP90) can interact with HIF-1alpha in vitro. Here we show that HSP90 also interacts with HIF-2alpha and HIF-3alpha, suggesting a general involvement of HSP90 in HIF-alpha stabilization. The PAS B domain, common to all three alpha subunits, was required for HSP90 interaction. ARNT competed with HSP90 for binding to the PAS B domain since an excess of either component inhibited the activity of the other. HSP90 as well as the heterocomplex members HSP70 and p23, but not HSP40, were detected in immunoprecipitations of endogenous cellular HIF-1alpha. While HSP90 and HSP70 bound to HIF-1alpha predominantly under normoxic conditions, ARNT bound to HIF-1alpha primarily under hypoxic conditions, suggesting that ARNT displaced HSP90 from HIF-1alpha following nuclear translocation. Hypoxic accumulation of HIF-1alpha was delayed in a novel cell model deficient for HSP90beta as well as after treatment of wild-type cells with the HSP90 inhibitor geldanamycin, suggesting that HSP90 activity is involved in the rapid HIF-1alpha protein induction. 相似文献
58.
Bettina Langhans Susann Schweitzer Ingrid Braunschweiger Monika Schulz Tilman Sauerbruch Ulrich Spengler 《Cytometry. Part A》2005,65(1):59-68
BACKGROUND: Hepatitis C virus (HCV)-derived lipopeptides can induce epitope-specific immune responses in lymphocytes from HCV-naive individuals. We analyzed whether such T cells generated by in vitro immunization with HCV core-derived lipopeptides exert HCV-specific cytolytic activity. METHODS: Using a sensitive flow cytometric cytotoxicity assay we characterized HCV-specific cytotoxicity in T cells generated in vitro with HCV core-derived 25-mer lipopeptides. In addition, we studied expressions of Fas ligand and perforin and interferon-gamma (IFN-gamma) secretion in HLA-A2-HCV(core_35-44) tetramer-positive T cells generated with lipopeptide amino acid 20-44 (LP20-44). RESULTS: CD8+ T cells induced in vitro with HCV core-derived lipopeptides only infrequently exerted HCV-specific cytotoxicity, irrespective of whether antigen-coated T2 cells or autologous B lymphoblasts were used as targets. Detailed analysis of HLA-A2-HCV(core_35-44) tetramer-positive T cells generated with LP20-44 revealed that in vitro immunization resulted in T cells that secreted IFN-gamma after antigen-specific restimulation and that upregulated expression of Fas ligand but not of perforin. CONCLUSIONS: Our data confirm at the functional level that HCV lipopeptides induce antigen-specific T lymphocytes that produce IFN-gamma but exert significant cytotoxicity in only a minority of experiments, probably because expression of cytolytic effector molecules is not enhanced in their granules. 相似文献
59.
Ruettger A Schueler S Mollenhauer JA Wiederanders B 《The Journal of biological chemistry》2008,283(2):1043-1051
Degradation of the extracellular matrix (ECM) is a prominent feature in osteoarthritis (OA), which is mainly because of the imbalance between anabolic and catabolic processes in chondrocytes resulting in cartilage and bone destruction. Various proteases act in concert to degrade matrix components, e.g. type II collagen, MMPs, ADAMTS, and cathepsins. Protease-generated collagen fragments may foster the destructive process. However, the signaling pathways associated with the action of collagen fragments on chondrocytes have not been clearly defined. The present data demonstrate that the N-terminal telopeptide of collagen type II enhances expression of cathepsins B, K, and L in articular chondrocytes at mRNA, protein, and activity levels, mediated at least in part through extracellular calcium. We also demonstrate that the induction is associated with the activation of protein kinase C and p38 MAP kinase. 相似文献
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