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61.
Fabian Schnitzler Matthias Friedrich Johannes Stallhofer Ulf Sch?nermarck Michael Fischereder Antje Habicht Nazanin Karbalai Christiane Wolf Marianne Angelberger Torsten Olszak Florian Beigel Cornelia Tillack Burkhard G?ke Reinhart Zachoval Gerald Denk Markus Guba Christian Rust Norbert Grüner Stephan Brand 《PloS one》2015,10(8)
Background
Currently, limited data of the outcome of inflammatory bowel disease (IBD) in patients after solid organ transplantation (SOT) are available. We aimed to analyze effects of SOT on the IBD course in a large IBD patient cohort.Methods
Clinical data from 1537 IBD patients were analyzed for patients who underwent SOT (n = 31) between July 2002 and May 2014. Sub-analyses included SOT outcome parameters, IBD activity before and after SOT, and efficacy of IBD treatment.Results
4.74% of patients with ulcerative colitis (UC) and 0.84% of patients with Crohn’s disease (CD) underwent SOT (p = 2.69 x 10−6, UC vs. CD). 77.4% of patients with SOT underwent liver transplantation (LTx) with tacrolimus-based immunosuppressive therapy after SOT. All LTx were due to primary sclerosing cholangitis (PSC) or PSC overlap syndromes. Six patients (19.4%) required renal transplantation and one patient (3.2%) heart transplantation. A survival rate of 83.9% after a median follow-up period of 103 months was observed. Before SOT, 65.0% of patients were in clinical remission and 5 patients received immunosuppressive therapy (16.1%). After SOT, 61.0% of patients were in remission (p = 1.00 vs. before SOT) and 29.0% required IBD-specific immunosuppressive or anti-TNF therapy (p = 0.54 vs. before SOT). 42.9% of patients with worsening of IBD after SOT were at higher risk of needing steroid therapy for increased IBD activity (p = 0.03; relative risk (RR): 10.29; 95% CI 1.26–84.06). Four patients (13.0%) needed anti-TNF therapy after SOT (response rate 75%).Conclusions
SOT was more common in UC patients due to the higher prevalence of PSC-related liver cirrhosis in UC. Despite mainly tacrolimus-based immunosuppressive regimens, outcome of SOT and IBD was excellent in this cohort. In this SOT cohort, concomitant immunosuppressive therapy due to IBD was well tolerated. 相似文献62.
Treatment with the chimerical monoclonal antibody rituximab results in CD20-directed B cell depletion. Although this depletion
is almost complete in the peripheral blood of nearly all patients with rheumatoid arthritis, a proportion of patients does
not exhibit a clinical response. The paper by Nakou and colleagues suggests that a decrease in CD19+CD27+ memory B cells in
both peripheral blood and bone marrow precedes the clinical response to rituximab. This finding adds to the emerging evidence
that lack of response to rituximab is associated with persistence of B lineage cells in specific body compartments. 相似文献
63.
64.
JH Shazia Fathima Jayaraman Selvaraj Venkatacalam Sivabalan Umapathy Vidhya Rekha Rajagopal Ponnulakshmi Veeraraghavan Vishnupriya Malathi Kullappan Radhika nalinakumari Sreekandan Surapaneni Krishna Mohan 《Bioinformation》2021,17(1):206
Matrix metalloproteinase protein-2 (MMP-2) is linked to the human oral squamous cell carcinoma. Therefore, it is of interest to design new inhibitors for MMP-2 to combat the disease. Thus, we document the molecular docking features of Aristolochic acid, Cryptopleurine, Epipodophyllotoxin, and Fagaronine with MMP-2 for further consideration. 相似文献
65.
Attachment of Sendai virus particles to cell membranes: dissociation of adsorbed virus particles with dithiothreitol. 下载免费PDF全文
Sendai virus particles bind to human erythrocytes at 4 degrees C and fuse with them at 37 degrees C. The present work describes a new method by which adsorbed virus particles can be removed from human erythrocytes, allowing quantitative determination of the number of virus particles which can bind and fuse with human erythrocyte membranes. Through the use of 125I-labeled Sendai virus particles, it is shown that incubation with 50 mM dithiothreitol removed about 90 to 95% of adsorbed virus particles. Fused virus particles were resistant to treatment with dithiothreitol. Negligible amounts of 125I-labeled Sendai virus particles were removed by treatment with dithiothreitol after incubation of virus-cell complexes at 37 degrees C. Trypsinized virus particles were able to attach to, but not fuse with, human erythrocytes even after prolonged incubation at 37 degrees C. Treatment with dithiothreitol removed as much as 80 to 85% of trypsinized virus particles incubated with human erythrocytes at 37 degrees C. A quantitative determination revealed that about 1,000 to 1,200 and 600 to 800 Sendai virus particles can bind to or fuse with human erythrocytes, respectively. 相似文献
66.
Sandra Stefanovic‐Barrett Anna S Dickson Stephen P Burr James C Williamson Ian T Lobb Dick JH van den Boomen Paul J Lehner James A Nathan 《EMBO reports》2018,19(5)
Misfolded or damaged proteins are typically targeted for destruction by proteasome‐mediated degradation, but the mammalian ubiquitin machinery involved is incompletely understood. Here, using forward genetic screens in human cells, we find that the proteasome‐mediated degradation of the soluble misfolded reporter, mCherry‐CL1, involves two ER‐resident E3 ligases, MARCH6 and TRC8. mCherry‐CL1 degradation is routed via the ER membrane and dependent on the hydrophobicity of the substrate, with complete stabilisation only observed in double knockout MARCH6/TRC8 cells. To identify a more physiological correlate, we used quantitative mass spectrometry and found that TRC8 and MARCH6 depletion altered the turnover of the tail‐anchored protein heme oxygenase‐1 (HO‐1). These E3 ligases associate with the intramembrane cleaving signal peptide peptidase (SPP) and facilitate the degradation of HO‐1 following intramembrane proteolysis. Our results highlight how ER‐resident ligases may target the same substrates, but work independently of each other, to optimise the protein quality control of selected soluble and tail‐anchored proteins. 相似文献
67.
Catherine C Beauheim Farrell Wymore Michael Nitzberg Zachariah K Zachariah Heng Jin JH Pate Skene Catherine A Ball Gavin Sherlock 《BMC bioinformatics》2007,8(1):338
Background
Biomedical ontologies are being widely used to annotate biological data in a computer-accessible, consistent and well-defined manner. However, due to their size and complexity, annotating data with appropriate terms from an ontology is often challenging for experts and non-experts alike, because there exist few tools that allow one to quickly find relevant ontology terms to easily populate a web form. 相似文献68.
Carbohydrate recognition by proteins is a key event in many biological
processes. Concanavalin A is known to specifically recognize the
pentasaccharide core (beta-GlcNAc-(1-->2)-alpha- Man-(1-->3)-[beta-
GlcNAc-(1-->2)-alpha-Man-(1-->6)]-Man) of N-linked oligosaccharides
with a Ka of 1.41 x 10(6 )M-1. We have determined the structure of
concanavalin A bound to beta-GlcNAc-(1-->2)-alpha-Man-(1-->3)-[beta-
GlcNAc-(1-->2)-alpha-Man- (1-->6)]-Man to 2.7A. In six of eight
subunits there is clear density for all five sugar residues and a well
ordered binding site. The pentasaccharide adopts the same conformation in
all eight subunits. The binding site is a continuous extended cleft on the
surface of the protein. Van der Waals interactions and hydrogen bonds
anchor the carbohydrate to the protein. Both GlcNAc residues contact the
protein. The GlcNAc on the 1-->6 arm of the pentasaccharide makes
particularly extensive contacts and including two hydrogen bonds. The
binding site of the 1-->3 arm GlcNAc is much less extensive.
Oligosaccharide recognition by Con A occurs through specific protein
carbohydrate interactions and does not require recruitment of adventitious
water molecules. The beta-GlcNAc-(1-->2)-Man glycosidic linkage PSI
torsion angle on the 1-->6 arm is rotated by over 50 degrees from that
observed in solution. This rotation is coupled to disruption of
interactions at the monosaccharide site. We suggest destabilization of the
monosaccharide site and the conformational strain reduces the free energy
liberated by additional interactions at the 1-->6 arm GlcNAc site.
相似文献
69.
70.
van Hoek AH; van Alen TA; Sprakel VS; Hackstein JH; Vogels GD 《Molecular biology and evolution》1998,15(9):1195-1206
The 18S and 5.8S rDNA genes and the internal transcribed spacers ITS-1 and
ITS-2 of ciliates living in the hindgut of frogs, millipedes, and
cockroaches were analyzed in order to study the evolution of intestinal
protists. All ciliates studied here belong to the genus Nycrotherus.
Phylogenetic analysis revealed that these ciliates from a monophyletic
group that includes the distantly related anaerobic free-living
heterotrichous ciliates Metopus palaeformis and Metopus contortus. The
intestinal ciliates from the different vertebrate and invertebrate hosts
are clearly divergent at the level of their rDNA repeats. This argues for
the antiquity of the associations and a predominantly vertical
transmission. This mode of transmission seems to be controlled primarily by
the behavior of the host. The different degrees of divergence between
ciliates living in different strains of one and the same cockroach species
most likely reflect the different geographical origins of the hosts. In
addition, host switches must have occurred during the evolution of
cockroaches, since identical ciliates were found only in distantly related
hosts. These phenomena prevent the reconstruction of potential cospeciation
events.
相似文献