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31.
Arends S Brouwer E van der Veer E Groen H Leijsma MK Houtman PM Th A Jansen TL Kallenberg CG Spoorenberg A 《Arthritis research & therapy》2011,13(3):R94
Introduction
Identifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-α) blocking therapy is important, especially in view of the costs and potential side effects of these agents. Recently, the AS Disease Activity Score (ASDAS) has been developed to assess both subjective and objective aspects of AS disease activity. However, data about the predictive value of the ASDAS with respect to clinical response to TNF-α blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-α blocking therapy in AS patients in daily clinical practice. 相似文献32.
Functional responses and scaling in predator-prey interactions of marine fishes: contemporary issues and emerging concepts 总被引:3,自引:0,他引:3
Hunsicker ME Ciannelli L Bailey KM Buckel JA Wilson White J Link JS Essington TE Gaichas S Anderson TW Brodeur RD Chan KS Chen K Englund G Frank KT Freitas V Hixon MA Hurst T Johnson DW Kitchell JF Reese D Rose GA Sjodin H Sydeman WJ van der Veer HW Vollset K Zador S 《Ecology letters》2011,14(12):1288-1299
Predator-prey interactions are a primary structuring force vital to the resilience of marine communities and sustainability of the world's oceans. Human influences on marine ecosystems mediate changes in species interactions. This generality is evinced by the cascading effects of overharvesting top predators on the structure and function of marine ecosystems. It follows that ecological forecasting, ecosystem management, and marine spatial planning require a better understanding of food web relationships. Characterising and scaling predator-prey interactions for use in tactical and strategic tools (i.e. multi-species management and ecosystem models) are paramount in this effort. Here, we explore what issues are involved and must be considered to advance the use of predator-prey theory in the context of marine fisheries science. We address pertinent contemporary ecological issues including (1) the approaches and complexities of evaluating predator responses in marine systems; (2) the 'scaling up' of predator-prey interactions to the population, community, and ecosystem level; (3) the role of predator-prey theory in contemporary fisheries and ecosystem modelling approaches; and (4) directions for the future. Our intent is to point out needed research directions that will improve our understanding of predator-prey interactions in the context of the sustainable marine fisheries and ecosystem management. 相似文献
33.
Mittempergher L de Ronde JJ Nieuwland M Kerkhoven RM Simon I Rutgers EJ Wessels LF Van't Veer LJ 《PloS one》2011,6(2):e17163
Background and Methods
Formalin Fixed Paraffin Embedded (FFPE) samples represent a valuable resource for cancer research. However, the discovery and development of new cancer biomarkers often requires fresh frozen (FF) samples. Recently, the Whole Genome (WG) DASL (cDNA-mediated Annealing, Selection, extension and Ligation) assay was specifically developed to profile FFPE tissue. However, a thorough comparison of data generated from FFPE RNA and Fresh Frozen (FF) RNA using this platform is lacking. To this end we profiled, in duplicate, 20 FFPE tissues and 20 matched FF tissues and evaluated the concordance of the DASL results from FFPE and matched FF material.Methodology and Principal Findings
We show that after proper normalization, all FFPE and FF pairs exhibit a high level of similarity (Pearson correlation >0.7), significantly larger than the similarity between non-paired samples. Interestingly, the probes showing the highest correlation had a higher percentage G/C content and were enriched for cell cycle genes. Predictions of gene expression signatures developed on frozen material (Intrinsic subtype, Genomic Grade Index, 70 gene signature) showed a high level of concordance between FFPE and FF matched pairs. Interestingly, predictions based on a 60 gene DASL list (best match with the 70 gene signature) showed very high concordance with the MammaPrint® results.Conclusions and Significance
We demonstrate that data generated from FFPE material with the DASL assay, if properly processed, are comparable to data extracted from the FF counterpart. Specifically, gene expression profiles for a known set of prognostic genes for a specific disease are highly comparable between two conditions. This opens up the possibility of using both FFPE and FF material in gene expressions analyses, leading to a vast increase in the potential resources available for cancer research. 相似文献34.
Goris MG Wagenaar JF Hartskeerl RA van Gorp EC Schuller S Monahan AM Nally JE van der Poll T van 't Veer C 《PloS one》2011,6(3):e18279
Background
Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. The bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. In general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. Not much is known about the innate immune response to leptospires during haematogenous dissemination. Previous work showed that a human THP-1 cell line recognized heat-killed leptospires and leptospiral LPS through TLR2 instead of TLR4. The LPS of virulent leptospires displayed a lower potency to trigger TNF production by THP-1 cells compared to LPS of non-virulent leptospires.Methodology/Principal Findings
We investigated the host response and killing of virulent and non-virulent Leptospira of different serovars by human THP-1 cells, human PBMC''s and human whole blood. Virulence of each leptospiral strain was tested in a well accepted standard guinea pig model. Virulent leptospires displayed complement resistance in human serum and whole blood while in-vitro attenuated non-virulent leptospires were rapidly killed in a complement dependent manner. In vitro stimulation of THP-1 and PBMC''s with heat-killed and living leptospires showed differential serovar and cell type dependence of cytokine induction. However, at low, physiological, leptospiral dose, living virulent complement resistant strains were consistently more potent in whole blood stimulations than the corresponding non-virulent complement sensitive strains. At higher dose living virulent and non-virulent leptospires were equipotent in whole blood. Inhibition of different TLRs indicated that both TLR2 and TLR4 as well as TLR5 play a role in the whole blood cytokine response to living leptospires.Conclusions/Significance
Thus, in a minimally altered system as human whole blood, highly virulent Leptospira are potent inducers of the cytokine response. 相似文献35.
M.?Rützler LJ?ZwiebelEmail author 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2005,191(9):777-790
Insects have an enormous impact on global public health as disease vectors and as agricultural enablers as well as pests and
olfaction is an important sensory input to their behavior. As such it is of great value to understand the interplay of the
molecular components of the olfactory system which, in addition to fostering a better understanding of insect neurobiology,
may ultimately aid in devising novel intervention strategies to reduce disease transmission or crop damage. Since the first
discovery of odorant receptors in vertebrates over a decade ago, much of our view on how the insect olfactory system might
work has been derived from observations made in vertebrates and other invertebrates, such as lobsters or nematodes. Together
with the advantages of a wide range of genetic tools, the identification of the first insect odorant receptors in Drosophila melanogaster in 1999 paved the way for rapid progress in unraveling the question of how olfactory signal transduction and processing occurs
in the fruitfly. This review intends to summarize much of this progress and to point out some areas where advances can be
expected in the near future. 相似文献
36.
37.
Absence of thrombin-activatable fibrinolysis inhibitor protects against sepsis-induced liver injury in mice 总被引:2,自引:0,他引:2
Renckens R Roelofs JJ ter Horst SA van 't Veer C Havik SR Florquin S Wagenaar GT Meijers JC van der Poll T 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(10):6764-6771
Thrombin-activatable fibrinolysis inhibitor (TAFI), also known as carboxypeptidase R, has been implicated as an important negative regulator of the fibrinolytic system. In addition, TAFI is able to inactivate inflammatory peptides such as complement factors C3a and C5a. To determine the role of TAFI in the hemostatic and innate immune response to abdominal sepsis, TAFI gene-deficient (TAFI-/-) and normal wild-type mice received an i.p. injection with Escherichia coli. Liver TAFI mRNA and TAFI protein concentrations increased during sepsis. In contrast to the presumptive role of TAFI as a natural inhibitor of fibrinolysis, TAFI-/- mice did not show any difference in E. coli-induced activation of coagulation or fibrinolysis, as measured by plasma levels of thrombin-anti-thrombin complexes and D-dimer and the extent of fibrin depositions in lung and liver tissues. However, TAFI-/- mice were protected from liver necrosis as indicated by histopathology and clinical chemistry. Furthermore, TAFI-/- mice displayed an altered immune response to sepsis, as indicated by an increased neutrophil recruitment to the peritoneal cavity and a transiently increased bacterial outgrowth together with higher plasma TNF-alpha and IL-6 levels. These data argue against an important part for TAFI in the regulation of the procoagulant-fibrinolytic balance in sepsis and reveals a thus far unknown role of TAFI in the occurrence of hepatic necrosis. 相似文献
38.
Renckens R Roelofs JJ Florquin S de Vos AF Lijnen HR van't Veer C van der Poll T 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(6):3735-3741
Matrix metalloproteinase (MMP)-9 is involved in extracellular matrix degradation and leukocyte migration. To determine the role of MMP-9 in the innate immune response to peritonitis, MMP-9 gene-deficient (MMP-9(-/-)) and normal wild-type mice were i.p. infected with Escherichia coli. MMP-9 mRNA and pro-MMP-9 protein levels increased rapidly upon induction of peritonitis. Although MMP-9(-/-) neutrophils showed a normal phagocytosis of E. coli in vitro, MMP-9(-/-) mice displayed a reduced resistance against E. coli peritonitis, as indicated by an enhanced bacterial outgrowth in the peritoneal cavity and increased dissemination of the infection. Furthermore, the cytokine response to LPS was not influenced by MMP-9 deficiency. However, during E. coli peritonitis, MMP-9(-/-) mice showed much higher peritoneal chemokine and cytokine levels compared with wild-type mice. Despite the increased local chemokine concentrations, MMP-9(-/-) mice displayed a diminished recruitment of leukocytes to the site of infection, indicating that cellular migration was impaired. Moreover, MMP-9(-/-) mice developed more severe distant organ damage during infection. These data suggest that MMP-9 is an essential component of an effective host response to E. coli peritonitis. 相似文献
39.
Renckens R Roelofs JJ Florquin S de Vos AF Pater JM Lijnen HR Carmeliet P van 't Veer C van der Poll T 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(2):1189-1196
Sepsis is associated with enhanced production of tissue-type plasminogen activator (tPA). We investigated the function of endogenous tPA in the immune responses to Escherichia coli-induced abdominal sepsis using tPA gene-deficient (tPA(-/-)) and normal wild-type (WT) mice. tPA(-/-) mice demonstrated an impaired defense against E. coli peritonitis as indicated by higher bacterial loads at the primary site of the infection, enhanced dissemination, and reduced survival. The protective function of tPA was independent of plasmin since plasminogen gene-deficient (Plg(-/-)) mice were indistinguishable from WT mice. Relative to WT mice, tPA(-/-) mice demonstrated similar neutrophil counts in the peritoneal cavity despite much higher bacterial loads and higher local concentrations of neutrophil attracting chemokines, suggesting a reduced migratory response. In line, tPA(-/-) mice demonstrated a reduced thioglycolate-induced neutrophil influx into the peritoneal cavity and i.p. injection of WT mice with a replication-defective adenoviral vector expressing tPA caused an enhanced cell migration to the peritoneal cavity during E. coli peritonitis. These findings identify a novel protective function of tPA in abdominal sepsis caused by E. coli that seems independent of its role in the generation of plasmin. 相似文献
40.
van Hall T Wolpert EZ van Veelen P Laban S van der Veer M Roseboom M Bres S Grufman P de Ru A Meiring H de Jong A Franken K Teixeira A Valentijn R Drijfhout JW Koning F Camps M Ossendorp F Kärre K Ljunggren HG Melief CJ Offringa R 《Nature medicine》2006,12(4):417-424
Defects in major histocompatibility complex (MHC) class I-restricted antigen presentation are frequently observed in human cancers and result in escape of tumors from cytotoxic T lymphocyte (CTL) immune surveillance in mice. Here, we show the existence of a unique category of CTLs that can prevent this escape. The CTLs target an alternative repertoire of peptide epitopes that emerge in MHC class I at the surface of cells with impaired function of transporter associated with antigen processing (TAP), tapasin or the proteasome. These peptides, although derived from self antigens such as the commonly expressed Lass5 protein (also known as Trh4), are not presented by normal cells. This explains why they act as immunogenic neoantigens. The newly discovered epitopes can be exploited for immune intervention against processing-deficient tumors through adoptive T-cell transfer or peptide vaccination. 相似文献