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101.
102.
AO Watts MMH van Lipzig WC Jaeger RM Seeber M van Zwam J Vinet MMC van der Lee M Siderius GJR Zaman HWGM Boddeke MJ Smit KDG Pfleger R Leurs HF Vischer 《British journal of pharmacology》2013,168(7):1662-1674
Background and Purpose
The C-X-C chemokine receptors 3 (CXCR3) and C-X-C chemokine receptors 4 (CXCR4) are involved in various autoimmune diseases and cancers. Small antagonists have previously been shown to cross-inhibit chemokine binding to CXCR4, CC chemokine receptors 2 (CCR2) and 5 (CCR5) heteromers. We investigated whether CXCR3 and CXCR4 can form heteromeric complexes and the binding characteristics of chemokines and small ligand compounds to these chemokine receptor heteromers.Experimental Approach
CXCR3–CXCR4 heteromers were identified in HEK293T cells using co-immunoprecipitation, time-resolved fluorescence resonance energy transfer, saturation BRET and the GPCR-heteromer identification technology (HIT) approach. Equilibrium competition binding and dissociation experiments were performed to detect negative binding cooperativity.Key Results
We provide evidence that chemokine receptors CXCR3 and CXCR4 form heteromeric complexes in HEK293T cells. Chemokine binding was mutually exclusive on membranes co-expressing CXCR3 and CXCR4 as revealed by equilibrium competition binding and dissociation experiments. The small CXCR3 agonist VUF10661 impaired binding of CXCL12 to CXCR4, whereas small antagonists were unable to cross-inhibit chemokine binding to the other chemokine receptor. In contrast, negative binding cooperativity between CXCR3 and CXCR4 chemokines was not observed in intact cells. However, using the GPCR-HIT approach, we have evidence for specific β-arrestin2 recruitment to CXCR3-CXCR4 heteromers in response to agonist stimulation.Conclusions and Implications
This study indicates that heteromeric CXCR3–CXCR4 complexes may act as functional units in living cells, which potentially open up novel therapeutic opportunities. 相似文献103.
Peter A. McCullough MD MPH Denise Barnard MD Robert Clare MS Stephen J. Ellis PhD Jerome L. Fleg MD Gregg C. Fonarow MD Barry A. Franklin PhD Ryan D. Kilpatrick PhD Dalane W. Kitzman MD Christopher M. O'Connor MD Ileana L. Piña MD MPH Udho Thadani MD Vinay Thohan MD David J. Whellan MD MHS for the HF‐ACTION Investigators 《Clinical cardiology》2013,36(10):611-620
104.
105.
Inge van den Akker-Scheek Jos JAM van Raay Inge HF Reininga Sjoerd K Bulstra Wiebren Zijlstra Martin Stevens 《BMC musculoskeletal disorders》2010,11(1):242
Background
Preoperative expectations of outcome of total hip and knee arthroplasty are important determinants of patients' satisfaction and functional outcome. Aims of the study were (1) to translate the Hospital for Special Surgery Hip Replacement Expectations Survey and Knee Replacement Expectations Survey into Dutch and (2) to study test-retest reliability and concurrent validity. 相似文献106.
107.
Increasing direct and indirect evidence suggests that erythropoietin (Epo) promotes both erythropoiesis and megakaryocytopoiesis. Here we report that, in mice infected with a recombinant spleen focus-forming retrovirus (SFFV) expressing an oncogenic erythropoietin receptor (EpoR), there was an increase in platelet count preceding the ensuing erythrocytosis. Concurrently, there was a substantial increase in splenic megakaryocytes. Culture of the bone marrow and spleen cells from infected mice showed enhanced numbers of multipotent megakaryocytic progenitors. DNA polymerase chain reaction analysis of individual megakaryocyte-containing colonies showed recombinant SFFV (SFFVcEpoR) proviral integration. Immunofluorescence of spleen sections showed overexpression of EpoR protein in the megakaryocytes. Mice infected with a strain of SFFV also developed splenic megakaryocytosis without activating overexpression of the EpoR in megakaryocytes. This in vivo system shows that a relationship between erythropoiesis and thrombopoiesis can exist at the level of the Epo-EpoR signaling pathway. Also, SFFV-based vectors may be excellent vehicles for the introduction of genes into multipotent, hematopoietic progenitors, in vitro. 相似文献
108.
The magnetic resonance (MR) and computed tomographic (CT) images of 53 patients with sinonasal tumors were analyzed and compared for accuracy in tumor mapping. the findings were confirmed by means of either surgery or biopsy. The MR images of 60 patients with inflammatory disease were also studied, and the findings were confirmed at surgery. Forty-seven additional MR images were also examined of patients with tumors showing histologic characteristics similar to those found in the sinonasal tumor group but occurring elsewhere in the head and neck, excluding the orbit. This study concludes that nearly 95% of sinonasal tumors have an intermediate T2 signal, while only 5% have bright T2 signals. This small latter group is composed almost exclusively of some minor salivary gland tumors and some neuromas. The inflammatory tissues all had bright T2 signals. The distinction between sinonasal tumors and inflammatory tissues was best accomplished with T2-weighted studies, and MR imaging was more accurate than CT. 相似文献
109.
110.
Macrofilaricides and onchocerciasis control, mathematical modelling of the prospects for elimination
William Soumbey Alley Gerrit J van Oortmarssen Boakye A Boatin Nico JD Nagelkerke Anton P Plaisier Jan HF Remme Janis Lazdins Gerard JJM Borsboom J Dik F Habbema 《BMC public health》2001,1(1):12-5