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41.
Using the non-ionic detergent dodecyl--D-maltoside we have developed a preparative method for the isolation of the 43 kDa, 47 kDa and D1-D2-Cyt b
559 species directly from thylakoid membranes. In contrast to previous procedures the photosynthetic membrane was exposed only to one mild detergent and that resulted in more stable preparations. The isolated species were examined spectroscopically and it was found that even under these mild conditions the D1-D2-Cyt b
559 did not retain the primary quinone QA.Abbreviations PS II
Photosystem II
- CF
Coupling Factor
- LHC
Light Harvesting Complex
- MES
4-morpholine-ethanesulfonic acid
- BIS-TRIS
2-[Bis (2-hydroxyethyl) amino]-2-hydroxymethyl-propane-1,3-diol
- SMN
0.4 M sucrose/50 mM MES (pH6)/10 mM NaCl 相似文献
42.
Bryan Smith Rocio Lledo-Garcia Kate L. Dixon Louis Christodoulou Matthew C. Catley 《MABS-AUSTIN》2018,10(7):1111-1130
Rozanolixizumab (UCB7665), a humanized high-affinity anti-human neonatal Fc receptor (FcRn) monoclonal antibody (IgG4P), has been developed to reduce pathogenic IgG in autoimmune and alloimmune diseases. We document the antibody isolation and compare rozanolixizumab with the same variable region expressed in various mono-, bi- and trivalent formats. We report activity data for rozanolixizumab and the different molecular formats in human cells, FcRn-transgenic mice, and cynomolgus monkeys. Rozanolixizumab, considered the most effective molecular format, dose-dependently and selectively reduced plasma IgG concentrations in an FcRn-transgenic mouse model (no effect on albumin). Intravenous (IV) rozanolixizumab dosing in cynomolgus monkeys demonstrated non-linear pharmacokinetics indicative of target-mediated drug disposition; single IV rozanolixizumab doses (30 mg/kg) in cynomolgus monkeys reduced plasma IgG concentration by 69% by Day 7 post-administration. Daily IV administration of rozanolixizumab (initial 30 mg/kg loading dose; 5 mg/kg daily thereafter) reduced plasma IgG concentrations in all cynomolgus monkeys, with low concentrations maintained throughout the treatment period (42 days). In a 13-week toxicology study in cynomolgus monkeys, supra-pharmacological subcutaneous and IV doses of rozanolixizumab (≤ 150 mg/kg every 3 days) were well tolerated, inducing sustained (but reversible) reductions in IgG concentrations by up to 85%, with no adverse events observed. We have demonstrated accelerated natural catabolism of IgG through inhibition of IgG:FcRn interactions in mice and cynomolgus monkeys. Inhibition of FcRn with rozanolixizumab may provide a novel therapeutic approach to reduce pathogenic IgG in human autoimmune disease. Rozanolixizumab is being investigated in patients with immune thrombocytopenia (NCT02718716) and myasthenia gravis (NCT03052751). 相似文献
43.
44.
Electrophoretic variants of nonspecific esterases (Est-6 and Est-C) of various populations of Drosophila melanogaster and Drosophila simulans from Northern Greece were studied by means of starch gel electrophoresis, and the results are compared with those obtained from standard stocks. Two new alleles of the Est-6 locus of D. melanogaster and two new alleles of the Est-6 locus of D. simulans are described. The position of the Est-C locus in D. simulans is estimated. Evidence is presented for the genetic homology of the Est-C locus of D. melanogaster and the Est-C locus of D. simulans. 相似文献
45.
Chaperone proteostasis in Parkinson's disease: stabilization of the Hsp70/α‐synuclein complex by Hip
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August Andersson Annemieke T van der Goot Shang‐Te Hsu Rafael Fernández‐Montesinos Jannie de Jong Tjakko J van Ham Ellen A Nollen David Pozo John Christodoulou Christopher M Dobson 《The EMBO journal》2009,28(23):3758-3770
The ATP‐dependent protein chaperone heat‐shock protein 70 (Hsp70) displays broad anti‐aggregation functions and has a critical function in preventing protein misfolding pathologies. According to in vitro and in vivo models of Parkinson's disease (PD), loss of Hsp70 activity is associated with neurodegeneration and the formation of amyloid deposits of α‐synuclein (αSyn), which constitute the intraneuronal inclusions in PD patients known as Lewy bodies. Here, we show that Hsp70 depletion can be a direct result of the presence of aggregation‐prone polypeptides. We show a nucleotide‐dependent interaction between Hsp70 and αSyn, which leads to the aggregation of Hsp70, in the presence of ADP along with αSyn. Such a co‐aggregation phenomenon can be prevented in vitro by the co‐chaperone Hip (ST13), and the hypothesis that it might do so also in vivo is supported by studies of a Caenorhabditis elegans model of αSyn aggregation. Our findings indicate that a decreased expression of Hip could facilitate depletion of Hsp70 by amyloidogenic polypeptides, impairing chaperone proteostasis and stimulating neurodegeneration. 相似文献
46.
Shang-Te Danny Hsu Lisa D. Cabrita John Christodoulou Christopher M. Dobson 《Biomolecular NMR assignments》2009,3(1):29-31
The gelation factor from Dictyostelium discoideum (ABP-120) is an actin binding protein consisting of six immunoglobulin (Ig) domains in the C-terminal rod domain. We have
recently used the pair of domains 5 and 6 of ABP-120 as a model system for studying multi-domain nascent chain folding on
the ribosome. Here we present the NMR assignments of domain 5 in its native and 8M urea-denatured states. 相似文献
47.
48.
Christopher A. Waudby Tuomas P.J. Knowles Jeremy N. Skepper John A. Carver John Christodoulou Sarah Meehan 《Biophysical journal》2010,98(5):843-851
αB-Crystallin is a small heat-shock protein (sHsp) that is colocalized with α-synuclein (αSyn) in Lewy bodies—the pathological hallmarks of Parkinson's disease—and is an inhibitor of αSyn amyloid fibril formation in an ATP-independent manner in vitro. We have investigated the mechanism underlying the inhibitory action of sHsps, and here we establish, by means of a variety of biophysical techniques including immunogold labeling and nuclear magnetic resonance spectroscopy, that αB-crystallin interacts with αSyn, binding along the length of mature amyloid fibrils. By measurement of seeded fibril elongation kinetics, both in solution and on a surface using a quartz crystal microbalance, this binding is shown to strongly inhibit further growth of the fibrils. The binding is also demonstrated to shift the monomer-fibril equilibrium in favor of dissociation. We believe that this mechanism, by which a sHsp interacts with mature amyloid fibrils, could represent an additional and potentially generic means by which at least some chaperones protect against amyloid aggregation and limit the onset of misfolding diseases. 相似文献
49.
50.
Michael S. Christodoulou Sandra Liekens Konstantinos M. Kasiotis Serkos A. Haroutounian 《Bioorganic & medicinal chemistry》2010,18(12):4338-4350
The synthesis of a series of novel trisubstituted pyrazole derivatives and their PIFA-mediated conversion to molecules bearing the fused pyrazolo[4,3-c]quinoline ring system is reported. The anti-angiogenic activity of these compounds was evaluated by using in vitro assays for endothelial cell proliferation and migration, and in the chicken chorioallantoic membrane (CAM) assay. Compounds containing the fused pyrazolo[4,3-c]quinoline motifs emerged as potent anti-angiogenic compounds, which also had the ability to inhibit the growth of human breast (MCF-7) and cervical (Hela) carcinoma cells in vitro. 相似文献