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排序方式: 共有412条查询结果,搜索用时 10 毫秒
1.
Daniel Jirák Jan Kríz Vít Herynek Benita Andersson Peter Girman Martin Burian Frantisek Saudek Milan Hájek 《Magnetic resonance in medicine》2004,52(6):1228-1233
A promising treatment method for type 1 diabetes mellitus is transplantation of pancreatic islets containing beta-cells. The aim of this study was to develop an MR technique to monitor the distribution and fate of transplanted pancreatic islets in an animal model. Twenty-five hundred purified and magnetically labeled islets were transplanted through the portal vein into the liver of experimental rats. The animals were scanned using a MR 4.7-T scanner. The labeled pancreatic islets were clearly visualized in the liver in both diabetic and healthy rats as hypointense areas on T2*-weighted MR images during the entire measurement period. Transmission electron microscopy confirmed the presence of iron-oxide nanoparticles inside the cells of the pancreatic islets. A significant decrease in blood glucose levels in diabetic rats was observed; normal glycemia was reached 1 week after transplantation. This study, therefore, represents a promising step toward possible clinical application in human medicine. 相似文献
2.
Charvat S Le Griel C Chignol MC Schmitt D Serres M 《Clinical & experimental metastasis》1999,17(8):677-685
Cell migration is an essential process in physiological and pathological conditions such as wound healing and tumor invasion.
This phenomenon involves cell adhesion on the extracellular matrix mediated by integrins, and cell detachment promoted in
part by metalloproteinases (MMPs). In the present study, the migration of two HaCaT-ras clones (metastatic or not), was compared with HaCaT cells, and normal human primary cultured keratinocytes. Using colloidal
gold migration assay, the migration index on type I and type IV collagen was similar for primary cultured keratinocytes and
HaCaT, whereas it was markedly higher for the HaCaT-ras clones. High motility of ras-transfected cells was confirmed from an in vitro wound healing assay. It was not correlated with changes in integrin expression or related to a different adhesion on extracellular
matrix. The Marismastat (BB-2516), a MMP inhibitor, inhibited in a dose-dependent effect the migration in both assays, demonstrating
the important role of MMPs in the migration process. Under our experimental conditions, MMP-1 activity was not detected in
HaCaT and MMP-9 activity was secreted by these cells only after their stimulation by EGF. Here, MMP-2 was the major gelatinolytic
activity secreted by all the cells and its secretion was markedly higher for HaCaT-ras clones compared with HaCaT. In addition, Western blotting results confirmed a higher expression of MMP-2 associated with
a lower expression of TIMP-2 in HaCaT-ras compared with HaCaT. These results suggest that Ha-ras oncogene could be a stimulating factor of migration and might modified the balance between MMP-2 and TIMP-2 in keratinocyte
cell lines.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
3.
Byron Peter R. Sun Zhuang Katayama Hirokazu Rypacek Frantisek 《Pharmaceutical research》1994,11(2):221-225
The pulmonary absorption kinetics of a single molecular weight distribution (MWD) of fluorophore-labeled poly-,-[N(2-hydroxyethyl)-DL-aspartamide] (F-PHEA), a hydrophilic and biocompatible synthetic polypeptide, were studied in the isolated, perfused rat lung (iprl) as functions of administered polymer concentration, dose, vehicle, and presence and absence of fluorophore. The MWD was characterized before and after absorption by measurement of weight- and number-averaged molecular weights (M
wand M
n, respectively) using high-performance gel-permeation chromatography. Values for M
w and M
n were 8.6 and 5.3 kD before, and 6.7 and 4.7 kD after, absorption into the perfusate; there was no significant metabolism and the MWD of the absorbed polymer was independent of both dose and sampling time over a 3-hr period. F-PHEA failed to show any evidence of aggregation in solution or changes in dose distribution within the airways as functions of increasing polymer concentration and dose. A concentration ranging study indicated the presence of a saturable, carrier-mediated transport process for F-PHEA with a maximum absorption rate, V
max, of approximately 180 µg or 0.027 µmol/hr. Coadministration of fluorophore-free PHEA was capable of depressing the absorption of F-PHEA. The transport process for F-PHEA appeared to have a molecular weight limit of about 7 kD for this hydrophilic polymer. 相似文献
4.
Michael B. Harbut Bhumit A. Patel Bryan K. S. Yeung Case W. McNamara A. Taylor Bright Jaime Ballard Frantisek Supek Todd E. Golde Elizabeth A. Winzeler Thierry T. Diagana Doron C. Greenbaum 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(52):21486-21491
Early secretory and endoplasmic reticulum (ER)-localized proteins that are terminally misfolded or misassembled are degraded by a ubiquitin- and proteasome-mediated process known as ER-associated degradation (ERAD). Protozoan pathogens, including the causative agents of malaria, toxoplasmosis, trypanosomiasis, and leishmaniasis, contain a minimal ERAD network relative to higher eukaryotic cells, and, because of this, we observe that the malaria parasite Plasmodium falciparum is highly sensitive to the inhibition of components of this protein quality control system. Inhibitors that specifically target a putative protease component of ERAD, signal peptide peptidase (SPP), have high selectivity and potency for P. falciparum. By using a variety of methodologies, we validate that SPP inhibitors target P. falciparum SPP in parasites, disrupt the protein’s ability to facilitate degradation of unstable proteins, and inhibit its proteolytic activity. These compounds also show low nanomolar activity against liver-stage malaria parasites and are also equipotent against a panel of pathogenic protozoan parasites. Collectively, these data suggest ER quality control as a vulnerability of protozoan parasites, and that SPP inhibition may represent a suitable transmission blocking antimalarial strategy and potential pan-protozoan drug target. 相似文献
5.
Introduction:Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening hemopoietic stem cell disorder characterized by the triad of hemolytic anemia, thrombosis, and impaired bone marrow function. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state.Patient concerns:A 27-year-old Caucasian man with PNH presented to the Emergency Department of our hospital with acute onset shortness of breath, cough and blood in urine.Diagnosis:The patient was diagnosed with acute hemolytic exacerbation of PNH complicated with moderate COVID19 pneumonia.Outcomes:The patient was initiated with an anticoagulant unfractionated heparin, dexamethasone, and cefuroxime injection. His symptoms quickly resolved, and he was discharged after 5 days.Conclusion:The complement system activation is a critical component in the sequalae of COVID19 infection. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state. Notably, C5a concentration was noted to be higher in patients with COVID19 infection. The use of complement inhibitors to attenuate immune mediated damage in COVID19 nevertheless represents a very interesting theoretical approach. However, careful consideration as to which patients may benefit will be required and the outcome of clinical trials needed. 相似文献
6.
7.
Normalizing Glutamine Concentration Causes Mitochondrial Uncoupling in an In Vitro Model of Human Skeletal Muscle 下载免费PDF全文
Adela Krajcova MD Jakub Ziak Katerina Jiroutkova MD Jana Patkova Moustafa Elkalaf MD Valer Dzupa MD PhD Jan Trnka MD PhD Frantisek Duska MD PhD 《JPEN. Journal of parenteral and enteral nutrition》2015,39(2):180-189
Background: Glutamine has been considered essential for rapidly dividing cells, but its effect on mitochondrial function is unknown. Materials and Methods: Human myoblasts were isolated from skeletal muscle biopsy samples (n = 9) and exposed for 20 days to 6 different glutamine concentrations (0, 100, 200, 300, 500, and 5000 µM). Cells were trypsinized and manually counted every 5 days. Seven days before the end of exposure, half of these cells were allowed to differentiate to myotubes. Afterward, energy metabolism in both myotubes and myoblasts was assessed by extracellular flux analysis (Seahorse Biosciences, Billerica, MA). The protocol for myoblasts was optimized in preliminary experiments. To account for different mitochondrial density or cell count, data were normalized to citrate synthase activity. Results: Fastest myoblast proliferation was observed at 300 µM glutamine, with a significant reduction at 0 and 100 µM. Glutamine did not influence basal oxygen consumption, anaerobic glycolysis or respiratory chain capacity. Glutamine significantly (P = .015) influenced the leak through the inner mitochondrial membrane. Efficiency of respiratory chain was highest at 200–300 µM glutamine (~90% of oxygen used for adenosine triphosphate synthesis). Increased glutamine concentration to 500 or 5000 µM caused mitochondrial uncoupling in myoblasts and myotubes, decreasing the efficiency of the respiratory chain to ~70%. Conclusion: Glutamine concentrations, consistent with moderate clinical hypoglutaminemia (300 µM), bring about an optimal condition of myoblast proliferation and for efficiency of aerobic phosphorylation in an in vitro model of human skeletal muscle. These data support the hypothesis of hypoglutaminemia as an adaptive phenomenon in conditions leading to bioenergetic failure (eg, critical illness). 相似文献
8.
The article discusses the issue of suitable parameters (pressures, recirculation and access flow) to assess hemodialysis vascular access quality (VAQ), available methods to measure those parameters and the setup of the entire VAQ surveillance system (VAQS) in a dialysis facility. Special attention is paid to factors which need some standardization to enable evaluation of VAQ trends in an individual as well as comparison of data from different patients and different dialysis facilities. The discussed procedures are documented with the authors' own measurement results and the results of the VAQS implemented in their unit. Both dynamic and static pressures exhibit insufficient sensitivity in detecting stenoses in native arteriovenous fistulas. Access recirculation is a late finding because with its non-zero value dialysis quality is already compromised. Timely and reliable detection of a deteriorating access condition is enabled by access flow (QVA) only. No standardization is needed in extracorporeal blood flow used in QVA evaluation by ultrasonic dilution. Multiple measurements may increase the reliability of thermodilutional measurements and are a must in optodilutional ones. Timing of the measurement during dialysis should be standardized. Measurement frequency should take into account access type, QVA value and access history. Shortened intervals are needed in the immediate post-intervention period with regard to risk of re-stenosis incidence and strongly nonlinear QVA decreases in such cases. A significant shift-over from surgical interventions to balloon angioplasties is to be expected with the introduction of a VAQS, and appropriate measures must be taken to ensure their quick availability. 相似文献
9.
Milos Chvapil Filip Kielar Frantisek Liska Alexandra Silhankova Klaus Brendel 《Connective tissue research》2013,54(4-5):242-250
This study extends the use of two lathyrogens, β-aminopropionitrile (BAPN) and D-penicillamine (DPA) from daily systemic or local-topical administration to long-time acting agents. This was achieved by converting the hydrophilic drugs into lipophilic derivatives. The synthesis of functional derivatives of DPA consisted in esterification with methyl-, hexyl-, or benzyl alcohols in the presence of thionylchloride. The esters formed were hydrochlorides, acidic and soluble in water. During neutralization in vitro or in vivo by tissue fluid, an oily substance is formed that elutes from a hydrogel polymer at a much slower rate than hydroplilic DPA itself. The degree of lipophilicity, measured as a partition coefficient between octanol/water, was highest for hexyl ester and lowest for methyl ester DPA. A single injection of either DPA hexyl ester HCl or 3-hexyl(amino) propionitrile into the full thickness skin incision wound in rats significantly lowered the breaking strength of the wound 12 days after injection, indicating the interference with collagen cross-linking. Both agents injected into the breast adenocarcinoma in Fisher rats significantly inhibited tumor growth without any signs of local or systemic toxicity. We conclude that these lipophilic lathyrogens with prolonged effectiveness are suitable in the treatment of pathologies, consisting of excessively cross-linked or deposited collagen (fibrotic adhesions, strictures, stenosis, and scar contractures) and in the treatment of single, solitary tumors, malignant and benign. 相似文献
10.
Coding variants of TLR2 and TLR4 genes do not substantially contribute to prosthetic joint infection