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101.
The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular
or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral
amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional
chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent
aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins
and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions
of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis
or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the
aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation
associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention. 相似文献
102.
Antigenic and genomic relationships among turkey and bovine enteric coronaviruses. 总被引:5,自引:0,他引:5 下载免费PDF全文
Antigenic and genomic relationships among tissue culture-adapted turkey enteric coronavirus (TCV) isolates, three strains of avian infectious bronchitis virus (IBV), and mammalian coronaviruses were investigated. Immunoblotting and immunoprecipitation experiments using polyclonal antisera showed that the four major structural proteins of TCV cross-reacted with the four homologous proteins of bovine enteric coronavirus (BCV), the N and M proteins of mouse hepatitis virus serotype 3, and the N protein of IBV. Close antigenic relationships between TCV and BCV were also established by seroneutralization and hemagglutination-inhibition. Of 49 monoclonal antibodies produced against either TCV or BCV, 11 differentiated the two viruses. Five of these monoclonal antibodies had neutralizing activities and were directed to either the peplomeric S (gp200-gp100) or hemagglutinin HE (gp140-gp65) glycoproteins. BCV cDNA probes tested on purified viral preparations and coronavirus-positive (by electron microscopy) fecal samples from diarrheic turkey poults confirmed the relatedness of TCV and BCV. The two viruses produced distinct cytopathic changes in HRT-18 cells in the presence of trypsin, whereas only TCV isolates were able to reproduce the clinical symptoms in turkey poults. Their matrix (M) proteins undergo different glycosylation processes. 相似文献
103.
Nicolaas A. M. Verbeek 《Journal of Ornithology》1988,129(4):449-456
Summary The mass gain, feather growth and development of a stable body temperature in nestlings of three ground nesting passerines — the Skylark (Alauda arvensis), Water Pipit (Anthus spinoletta) and Wheatear (Oenanthe oenanthe) — were studied in the alpine meadows of the western Pyrenees. When left together in the nest, individual Skylark nestlings had a stable body temperature of about 39°C by day 5, Water Pipits by day 6–7 and Wheatears by day 7–8. Individual nestlings, taken out of the nest and exposed to low ambient temperatures, could maintain a high body temperature (90% of adult levels) at an age of between 7 and 8 days (Skylark), and 10 and 11 days (Water Pipit and Wheatear, respectively). Feather growth was fastest in Skylarks. As the young in this species sit in exposed nests, early growth of feathers may help to retain heat or exclude solar radiation depending on the ambient conditions. Body mass gain is fastest in Skylarks and slowest in Wheatears and Water Pipits, which correlates with their nesting mode. All three species attain half their fledging weight between 4.2 and 5.0 days, regardless how long they remain in the nest subsequently.
Zusammenfassung Massenzunahme, Federwachstum und Entwicklung einer konstanten Körpertemperatur wurde bei den Nestlingen dreier bodenbrütender Singvögel in den alpinen Matten der westlichen Pyrenäen untersucht, nämlich bei Feldlerche, Wasserpieper und Steinschmätzer. Wenn die Jungen zusammen im Nest bleiben, erreichen Feldlerchen am 5., Wasserpieper am 6.–7. und Steinschmätzer am 7. bis 8. Tag eine konstante Körpertemperatur von etwa 39°C. Einzelne aus dem Nest genommene und niedriger Umgebungstemperatur ausgesetzte Junge können eine hohe Körpertemperatur (etwa 90% der ad.) im Alter von 7–8 (Feldlerche) bzw. von 10–11 Tagen (Wasserpieper, Steinschmätzer) aufrecht erhalten. Das Federwachstum war bei der Feldlerche am schnellsten. Da bei dieser Art die Jungen in offenen Nestern sitzen, dürfte ein frühes Federwachstum eine hohe Bedeutung für die Isolation des Körpers gegenüber der Umgebung besitzen. Die Zunahme der Körpermasse ist bei der Feldlerche rascher als bei Wasserpieper und Steinschmätzer. Die Hälfte der Körpermasse zum Zeitpunkt des Ausfliegens wird bei allen drei Arten im Alter von 4,2 bis 5,0 Tagen erreicht, unabhängig von der Länge der Nestlingszeit.相似文献
104.
Veninga H Becker S Hoek RM Wobus M Wandel E van der Kaa J van der Valk M de Vos AF Haase H Owens B van der Poll T van Lier RA Verbeek JS Aust G Hamann J 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(9):6574-6583
The heptahelical receptor CD97 is a defining member of the EGF-TM7 family of adhesion class receptors. In both humans and mice, CD97 isoforms are expressed with variable numbers of tandemly arranged N-terminal epidermal growth factor-like domains that facilitate interactions with distinct cellular ligands. Results from treatment of mice with mAbs in various disease models have suggested a role for CD97 in leukocyte trafficking. Here, we aimed to thoroughly characterize the expression profile of CD97, and delineate its biological function. To this end, we applied a novel polyclonal Ab, which is the first antiserum suitable for immunohistochemistry, and combined this analysis with the study of Cd97-lacZ knock-in mice. We show that similar to the situation in humans, hematopoietic, epithelial, endothelial, muscle, and fat cells expressed CD97. Despite this broad expression pattern, the Cd97(-/-) mouse that we created had no overt phenotype, except for a mild granulocytosis. Furthermore, granulocyte accumulation at sites of inflammation was normal in the absence of CD97. Interestingly, application of CD97 mAbs blocked granulocyte trafficking after thioglycollate-induced peritonitis in wild-type but not in knock-out mice. Hence, we conclude that CD97 mAbs actively induce an inhibitory effect that disturbs normal granulocyte trafficking, which is not perturbed by the absence of the molecule. 相似文献
105.
Bert van der Zwaag Lude Franke Martin Poot Ron Hochstenbach Henk A. Spierenburg Jacob A. S. Vorstman Emma van Daalen Maretha V. de Jonge Nienke E. Verbeek Eva H. Brilstra Ruben van 't Slot Roel A. Ophoff Michael A. van Es Hylke M. Blauw Jan H. Veldink Jacobine E. Buizer-Voskamp Frits A. Beemer Leonard H. van den Berg Cisca Wijmenga Hans Kristian Ploos van Amstel Herman van Engeland J. Peter H. Burbach Wouter G. Staal 《PloS one》2009,4(5)
The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD), and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD. 相似文献
106.
Rodriguez W Mold C Kataranovski M Hutt JA Marnell LL Verbeek JS Du Clos TW 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(1):530-538
C-reactive protein (CRP) is a member of the pentraxin family of proteins and an acute phase reactant. CRP modulates the response to inflammatory stimuli including LPS and C5a. We recently demonstrated that CRP prevents and reverses proteinuria in accelerated nephrotoxic nephritis (NTN). NTN is a model of active inflammatory immune complex-mediated nephritis induced by injection of antiglomerular basement membrane. CRP treatment prevented the induction of NTN in C57BL/6 (B6) mice, increased survival, and reversed ongoing nephritis. Protection was associated with a decrease in IL-1beta and chemokines in the kidney and peritoneal cells as measured by quantitative RT-PCR. However, IL-10(-/-) mice were not protected by CRP either when given before disease onset or when disease activity was maximal. FcgammaRI(-/-) mice developed NTN, but were only transiently protected by CRP treatment. This transient protection was abrogated by cobra venom factor depletion of complement from FcgammaRI(-/-) mice. However, complement depletion did not prevent CRP-mediated protection in B6 mice, and CRP was protective in C3(-/-) mice. The role of macrophages in the protection provided by CRP was tested by treating B6 mice with liposomes containing clodronate. Clodronate-containing liposomes deplete mice of splenic and hepatic macrophages for 5-7 days. Pretreatment of NTN mice with clodronate but not control liposomes completely prevented CRP-mediated protection. These studies suggest that CRP mediates protection from NTN through the induction of IL-10 and that macrophages are required. In addition, FcgammaRI plays an important role but is not the sole mediator of CRP-mediated protection. 相似文献
107.
Sara Reynhout Sandra Jansen Dorien Haesen Siska van Belle Sonja A. de Munnik Ernie M.H.F. Bongers Jolanda H. Schieving Carlo Marcelis Jeanne Amiel Marlène Rio Heather Mclaughlin Roger Ladda Susan Sell Marjolein Kriek Cacha M.P.C.D. Peeters-Scholte Paulien A. Terhal Koen L. van Gassen Nienke Verbeek Lisenka E.L.M. Vissers 《American journal of human genetics》2019,104(2):357
108.
Monocyte-derived, fibroblast-like cells called fibrocytes are associated with fibrotic lesions. The plasma protein serum amyloid P component (SAP; also known as pentraxin-2, PTX2) inhibits fibrocyte differentiation in vitro, and injections of SAP inhibit fibrosis in vivo. SAP is a member of the pentraxin family of proteins that includes C-reactive protein (CRP; PTX1) and pentraxin-3 (PTX3). All three pentraxins are associated with fibrosis, but only SAP and CRP have been studied for their effects on fibrocyte differentiation. We find that compared to SAP and CRP, PTX3 promotes human and murine fibrocyte differentiation. The effect of PTX3 is dependent on FcγRI. In competition studies, the fibrocyte-inhibitory activity of SAP is dominant over PTX3. Binding competition studies indicate that SAP and PTX3 bind human FcγRI at different sites. In murine models of lung fibrosis, PTX3 is present in fibrotic areas, and the PTX3 distribution is associated with collagen deposition. In lung tissue from pulmonary fibrosis patients, PTX3 has a widespread distribution, both in unaffected tissue and in fibrotic lesions, whereas SAP is restricted to areas adjacent to vessels, and absent from fibrotic areas. These data suggest that the relative levels of SAP and PTX3 present at sites of fibrosis may have a significant effect on the ability of monocytes to differentiate into fibrocytes. 相似文献
109.
Validation of soluble amyloid‐β precursor protein assays as diagnostic CSF biomarkers for neurodegenerative diseases 下载免费PDF全文
Linda J.C. van Waalwijk van Doorn Marleen J. Koel‐Simmelink Ute Haußmann Hans Klafki Hanne Struyfs Philipp Linning Hans‐Joachim Knölker Harry Twaalfhoven H. Bea Kuiperij Sebastiaan Engelborghs Philip Scheltens Marcel M. Verbeek Eugeen Vanmechelen Jens Wiltfang Charlotte E. Teunissen 《Journal of neurochemistry》2016,137(1):112-121
110.
Ding JW Zhou T Zeng H Ma L Verbeek JS Yin D Shen J Chong AS 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(1):261-268
We have previously reported that anti-Gal-alpha1,3Gal (Gal) IgG3 mAbs mediate a classical complement-dependent hyperacute rejection (HAR), while anti-Gal IgG1 mAbs mediate HAR that is dependent on complement, the Fc-gamma receptors FcgammaRII/III (CD32/CD16), and NK cells. IgG2a and IgG2b subclasses can activate complement and have FcgammaR binding properties in vitro. Whether these IgG subclasses can mediate HAR in vivo and the mechanisms by which they would do so are not known. In this study, we isolated spontaneous IgG switch mutants from an anti-Gal IgG1 hybridoma. In vitro complement-mediated hemolytic assays with mouse complement indicate that both anti-Gal IgG2a and IgG2b mAbs were more potent compared with the parent anti-Gal IgG1. In vivo administration of anti-Gal IgG2a and IgG2b mAbs into Gal-/- mice induced HAR of rat cardiac xenografts. HAR induced by anti-Gal IgG2a and IgG2b was dependent on complement activation and the presence of NK cells. Using FcgammaRIII-deficient (Gal-/-CD16-/-) recipients, we observed that HAR mediated by different anti-Gal IgG subclasses was variably dependent on FcgammaRIII, with IgG1>IgG2b>IgG2a=IgG3. Using FcgammaRI-deficient (Gal-/-CD64-/-) recipients, we observed that HAR mediated by anti-Gal IgG1, IgG2a, and IgG2b, but not by anti-Gal IgG3, was dependent on FcgammaRI. Collectively, these studies demonstrate the necessity and sufficiency of complement in IgG3-mediated HAR and the necessity of both complement and FcgammaR, especially FcgammaRI, in IgG1-, IgG2a-, and IgG2b-mediated HAR. 相似文献