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1.
Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes 总被引:8,自引:0,他引:8 下载免费PDF全文
Bamberger C Schärer A Antsiferova M Tychsen B Pankow S Müller M Rülicke T Paus R Werner S 《The American journal of pathology》2005,167(3):733-747
The transforming growth factor-beta family member activin is a potent regulator of skin morphogenesis and repair. Transgenic mice overexpressing activin in keratinocytes display epidermal hyper-thickening and dermal fibrosis in normal skin and enhanced granulation tissue formation after wounding. Mice overexpressing the secreted activin antagonist follistatin, however, have the opposite wound-healing phenotype. To determine whether activin affects skin morphogenesis and repair via activation of keratinocytes and/or stromal cells, we generated transgenic mice expressing a dominant-negative activin receptor IB mutant (dnActRIB) in keratinocytes. The architecture of adult skin was unaltered in these mice, but delays were observed in postnatal pelage hair follicle morphogenesis and in the first catagen-telogen transformation of hair follicles. Although dnActRIB-transgenic mice showed slightly delayed wound re-epithelialization after skin injury, the strong inhibition of granulation tissue formation seen in follistatin-transgenic mice was not observed. Therefore, although endogenous activin appeared to affect skin morphogenesis and repair predominantly via stromal cells, overexpressed activin strongly affected the epidermis. The epidermal phenotype of activin-overexpressing mice was partially rescued by breeding these animals with dnActRIB-transgenic mice. These results demonstrate that activin affects both stromal cells and keratinocytes in normal and wounded skin and that the effect on keratinocytes is dose-dependent in vivo. 相似文献
2.
The purpose of this study was to quantify to what extent relative and absolute bladder dose-volume and dose-surface histograms of the planning CT scan were representative for the actual treatment. We used data of 17 patients, who each received 11 repeat CT scans and a planning CT scan. The repeat CT scans were matched on the planning CT scan by the bony anatomy. Clinical treatment plans were used to evaluate the impact of bladder filling changes on the four histogram types. The impact was quantified by calculating for this patient group the correlation coefficient between the planning histogram and the treatment histogram. We found that the absolute dose-surface histogram was the most representative one for the actual treatment. 相似文献
3.
Katrien De Jaeger Mischa S Hoogeman Martijn Engelsman Yvette Seppenwoolde Eugène M F Damen Ben J Mijnheer Liesbeth J Boersma Joos V Lebesque 《Radiotherapy and oncology》2003,69(1):1-10
BACKGROUND AND PURPOSE: The low density of lung tissue causes a reduced attenuation of photons and an increased range of secondary electrons, which is inaccurately predicted by the algorithms incorporated in some commonly available treatment planning systems (TPSs). This study evaluates the differences in dose in normal lung tissue computed using a simple and a more correct algorithm. We also studied the consequences of these differences on the dose-effect relations for radiation-induced lung injury. MATERIALS AND METHODS: The treatment plans of 68 lung cancer patients initially produced in a TPS using a calculation model that incorporates the equivalent-path length (EPL) inhomogeneity-correction algorithm, were recalculated in a TPS with the convolution-superposition (CS) algorithm. The higher accuracy of the CS algorithm is well-established. Dose distributions in lung were compared using isodoses, dose-volume histograms (DVHs), the mean lung dose (MLD) and the percentage of lung receiving >20 Gy (V20). Published dose-effect relations for local perfusion changes and radiation pneumonitis were re-evaluated. RESULTS: Evaluation of isodoses showed a consistent overestimation of the dose at the lung/tumor boundary by the EPL algorithm of about 10%. This overprediction of dose was also reflected in a consistent shift of the EPL DVHs for the lungs towards higher doses. The MLD, as determined by the EPL and CS algorithm, differed on average by 17+/-4.5% (+/-1SD). For V20, the average difference was 12+/-5.7% (+/-1SD). For both parameters, a strong correlation was found between the EPL and CS algorithms yielding a straightforward conversion procedure. Re-evaluation of the dose-effect relations showed that lung complications occur at a 12-14% lower dose. The values of the TD(50) parameter for local perfusion reduction and radiation pneumonitis changed from 60.5 and 34.1 Gy to 51.1 and 29.2 Gy, respectively. CONCLUSIONS: A simple tissue inhomogeneity-correction algorithm like the EPL overestimates the dose to normal lung tissue. Dosimetric parameters for lung injury (e.g. MLD, V20) computed using both algorithms are strongly correlated making an easy conversion feasible. Dose-effect relations should be refitted when more accurate dose data is available. 相似文献
4.
Husmann L Wiegand M Valenta I Gaemperli O Schepis T Siegrist PT Namdar M Wyss CA Alkadhi H Kaufmann PA 《The international journal of cardiovascular imaging》2008,24(5):511-518
Objective The aim of this study was to compare the diagnostic accuracy of myocardial perfusion imaging (MPI) by positron emission tomography
(PET) with the diagnostic accuracy of MPI by single photon emission computed tomography (SPECT) in two comparable patient
cohorts, using coronary angiography (CA) as the standard of reference. Methods A “SPECT-group” of 80 patients (15 female, 65 male; mean age 60 ± 9 years) and a “PET-group” of 70 patients (14 female, 56
male; mean age 57 ± 10 years) underwent a one day stress/rest examination either with attenuation-corrected 13N-ammonia PET or attenuation-corrected 201TlCl SPECT or 99mTc-hexakis-methoxy-isobutyl-isonitril (MIBI) SPECT. PET and SPECT results were semiquantitatively graded using a 6-segment
heart model. All patients underwent CA, and stenoses were graded as a diameter reduction ≥50%. Results Coronary findings between both groups did not significantly differ at CA. For the SPECT-group overall sensitivity and specificity
for localisation of stenoses was 77% and 84%. Respective values for the PET-group were 97% and 84%. The specificity of MPI
by SPECT in the detection of ischemia was 74% and 91% for MPI by PET. The diagnostic accuracy of MPI improves when the individual
coronary dominance and previous coronary revascularisations are taken into account. Conclusion MPI by 13N-ammonia PET is more sensitive in the detection and localisation of coronary stenoses, and more specific in the detection
of ischemia than MPI by 201TlCl/99mMIBI SPECT. 相似文献
5.
Liu J Yang C Simpson C Deryckere D Van Deusen A Miley MJ Kireev D Norris-Drouin J Sather S Hunter D Korboukh VK Patel HS Janzen WP Machius M Johnson GL Earp HS Graham DK Frye SV Wang X 《ACS medicinal chemistry letters》2012,3(2):129-134
Ectopic Mer expression promotes pro-survival signaling and contributes to leukemogenesis and chemoresistance in childhood acute lymphoblastic leukemia (ALL). Consequently, Mer kinase inhibitors may promote leukemic cell death and further act as chemosensitizers increasing efficacy and reducing toxicities of current ALL regimens. We have applied a structure-based design approach to discover novel small molecule Mer kinase inhibitors. Several pyrazolopyrimidine derivatives effectively inhibit Mer kinase activity at sub-nanomolar concentrations. Furthermore, the lead compound shows a promising selectivity profile against a panel of 72 kinases and has excellent pharmacokinetic properties. We also describe the crystal structure of the complex between the lead compound and Mer, opening new opportunities for further optimization and new template design. 相似文献
6.
Christina Schaub Mischa Uebachs Heinz Beck Michael Linnebank 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2013,225(4):527-534
Homocystinuria is an inborn error of metabolism characterized by plasma homocysteine levels up to 500 μM, premature vascular events and mental retardation. Mild elevations of homocysteine plasma levels up to 25 μM, which are common in the general population, are associated with vascular disease, cognitive impairment and neurodegeneration. Several mechanisms of homocysteine neurotoxicity have been investigated. However, information on putative effects of hyperhomocysteinemia on the electrophysiology of neurons is limited. To screen for such effects, we examined primary cultures of mouse hippocampal neurons with the whole-cell patch-clamp technique. Homocysteine was applied intracellularly (100 μM), or cell cultures were incubated with 100 μM homocysteine for 24 h. Membrane voltage was measured in current-clamp mode, and action potential firing was induced with short and prolonged current injections. Single action potentials induced by short current injections (5 ms) were not altered by acute application or incubation of homocysteine. When we elicited trains of action potentials with prolonged current injections (200 ms), a broadening of action potentials during repetitive firing was observed in control neurons. This spike broadening was unaltered by acute application of homocysteine. However, it was significantly diminished when incubation with homocysteine was extended to 24 h prior to recording. Furthermore, the number of action potentials elicited by low current injections was reduced after long-term incubation with homocysteine, but not by the acute application. After 24 h of homocysteine incubation, the input resistance was reduced which might have contributed to the observed alterations in membrane excitability. We conclude that homocysteine exposure causes changes in the intrinsic electrophysiological properties of cultured hippocampal neurons as a mechanism of neurological symptoms of hyperhomocysteinemia. 相似文献
7.
Pape A Kutschker S Kertscho H Stein P Horn O Lossen M Zwissler B Habler O 《Critical care (London, England)》2012,16(2):R69
ABSTRACT: INTRODUCTION: The correction of hypovolemia with acellular fluids results in acute normovolemic anemia. Whether the choice of the infusion fluid has an impact on the maintenance of oxygen (O2) supply during acute normovolemic anemia has not been investigated so far. METHODS: Thirty-six anesthetized and mechanically ventilated pigs were hemodiluted to their physiological limit of anemia tolerance, reflected by the individual critical hemoglobin concentration (Hbcrit). Hbcrit was defined as the Hb-concentration corresponding with the onset of supply-dependency of total body O2-consumption (VO2). The hemodilution protocol was randomly performed with either tetrastarch (6% HES 130/0.4, TS-group, n = 9), gelatin (3.5% urea-crosslinked polygeline, GEL-group, n = 9), hetastarch (6% HES 450/0.7, HS-group, n = 9) or Ringer's solution (RS-group, n = 9). The primary endpoint was the dimension of Hbcrit, secondary endpoints were parameters of central hemodynamics, O2 transport and tissue oxygenation. RESULTS: In each animal, normovolemia was maintained throughout the protocol. Hbcrit was met at 3.7 ± 0.6 g/dl (RS), 3.0 ± 0.6 g/dl (HS P < 0.05 vs. RS), 2.7 ± 0.6 g/dl (GEL, P < 0.05 vs. RS) and 2.1 ± 0.4 g/dl (TS, P < 0.05 vs. GEL, HS and RS). Hemodilution with RS resulted in a significant increase of extravascular lung water index (EVLWI) and a decrease of arterial oxygen partial pressure (paO2), and O2 extraction ratio was increased, when animals of the TS-, GEL- and HS-groups met their individual Hbcrit. CONCLUSIONS: The choice of the intravenous fluid has an impact on the tolerance of acute normovolemic anemia induced by acellular volume replacement. Third-generation tetrastarch preparations (e.g., HES 130/0.4) appear most advantageous regarding maintenance of tissue oxygenation during progressive anemia. The underlying mechanism includes a lower degree of extravasation and favourable effects on microcirculatory function. 相似文献
8.
Gabriela Melo Rodriguez James Bowen Mischa Zelzer Artemis Stamboulis 《RSC advances》2020,10(30):17642
The surface of a medical implant is required to interact favourably with ions, biomolecules and cells in vivo, commonly resulting in the formation of the extracellular matrix. Medical grade Ti6Al4V alloy is widely used in orthopaedic and dental applications for bone replacement due to its advantageous mechanical properties and biocompatibility, which enhances the adhesion between native tissue and the implanted material. In this study, chemical and thermal modification of a medical-grade Ti6Al4V alloy were performed to enhance electrostatic interactions at the alloy surface with a synthetic peptide, suitable for conferring drug release capabilities and antimicrobial properties. The modified surfaces exhibited a range of topographies and chemical compositions depending primarily on the treatment temperature. The surface wetting behaviour was found to be pH-dependent, as were the adhesive properties, evidenced by chemical force titration atomic force microscopy.The surface of a medical implant is required to interact favourably with ions, biomolecules and cells in vivo, commonly resulting in the formation of the extracellular matrix. 相似文献
9.
10.
Jing Liu Chao Yang Catherine Simpson Deborah DeRyckere Amy Van Deusen Michael J. Miley Dmitri Kireev Jacqueline Norris-Drouin Susan Sather Debra Hunter Victoria K. Korboukh Hari S. Patel William P. Janzen Mischa Machius Gary L. Johnson H. Shelton Earp Douglas K. Graham Stephen V. Frye Xiaodong Wang 《ACS medicinal chemistry letters》2014,5(10):1173