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Skokos EA Charokopos A Khan K Wanjala J Kyriakides TR 《The American journal of pathology》2011,178(5):2311-2321
Homotypic cell fusion occurs in several cell types including macrophages in the formation of foreign body giant cells. Previously, monocyte chemoattractant protein-1 (MCP-1) was demonstrated to be required for foreign body giant cell formation in the foreign body response. The present study investigated the fusion defect in MCP-1-null macrophages by implanting biomaterials intraperitoneally in wild-type and MCP-1-null mice and monitoring the macrophage response at 12 hours to 4 weeks. MCP-1-null mice exhibited reduced accumulation and fusion of macrophages on implants, which was associated with attenuation of the foreign body response. Consistent with previous in vitro findings, the level of matrix metalloproteinase-9 (MMP-9) was reduced in MCP-1-null macrophages adherent to implants. In contrast, CCR2 expression was unaffected. In vitro studies revealed reduced tumor necrosis factor-α (TNF-α) production and abnormal subcellular redistribution of E-cadherin and β-catenin during fusion in MCP-1-null macrophages. Exogenous TNF-α caused an increase in the production of MMP-9 and rescued the fusion defect. Addition of GM6001 (MMP inhibitor) or NSC23766 (Rac1 inhibitor) indicated two distinct induction pathways, one for E-cadherin/β-catenin and one for MCP-1, TNF-α, and MMP-9. Considered together, these observations demonstrate that induction of E-cadherin/β-catenin is not sufficient for fusion in the absence of MCP-1 or the downstream mediators TNF-α and MMP-9. Moreover, attenuation of the foreign body response in intraperitoneal implants in MCP-1-null mice demonstrates that the process depends on tissue-specific factors. 相似文献
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Abdulkarim K Ridell B Johansson P Kutti J Safai-Kutti S Andréasson B 《European journal of haematology》2011,86(2):148-155
The Philadelphia chromosome-negative (Ph-) chronic myeloproliferative neoplasms include the three well-known clinical entities polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Over time, patients with ET and PV may develop myelofibrosis (MF), and all three entities carry a risk of transformation into acute myeloid leukemia (AML). In a population-based survey during 1983-1999, we studied a total of 358 patients who were diagnosed with ET and PV in the city of Gothenburg, Sweden. At the time of diagnosis, evaluable bone marrow biopsy material was available from 280 of these patients. The current work was aimed at investigating the impact of peripheral blood counts, spleen size, and bone marrow biopsy findings at diagnosis on long-term survival and the risk of development of AML or MF in this well-defined unselected population. The variables evaluated were venous blood hemoglobin concentration, packed cell volume, white blood cell count, platelet count, and splenic enlargement; as to bone marrow biopsies, interest was focused on reticulin content, focal or generalized collagen formation, bone marrow cellularity, and megakaryocyte profile number. Over the median observation time of 15 yr, the patients with ET did not demonstrate any significant difference as to survival compared to the normal Swedish population (hazard ratio, 1.23; 95% confidence interval, 0.97-1.51; p= 0.089). The patients with PV, on the other hand, had a significantly shorter survival compared to general population (hazard ratio, 1.66; 95% confidence interval, 1.38-1.99; p< 0.001). A lower hemoglobin concentration at diagnosis of ET predicted poorer survival (p =0.0281), whereas patients with PV with splenic enlargement at diagnosis had a shorter survival (p =0.037). In the patients with ET, the risk of transformation to either MF or AML was significantly associated with low hemoglobin concentration and high white cell count at diagnosis (p =0.0037 and 0.0306, respectively). An increased reticulin content and hypercellularity in the bone marrow at diagnosis were also independent risk factors (p =0.0359 and 0.0103, respectively). The risk of transformation in patients with PV was significantly associated with splenic enlargement and increase in bone marrow reticulin content (p =0.0028 and 0.0164, respectively). 相似文献
86.
Faten Limaiem Selma Bellil Khadija Bellil Inès Chelly Amina Mekni Moncef Khaldi Slim Haouet Moncef Zitouna Nidhameddine Kchir 《Clinical neurology and neurosurgery》2010
Objective
To analyze epidemiological characteristics, clinical symptoms, radiological aspects, treatment and outcome of central nervous system hydatidosis and compare our results with those reported in literature.Patients and methods
In our retrospective study, we reviewed 39 cases of primary central nervous system hydatid cysts operated on in our hospital between 1998 and 2007.Results
There were 20 male and 19 female patients (sex-ratio M/F = 1.05) between 2 and 68 years of age (mean = 26.5 years). Thirteen of the patients were children (33.3%) with a mean age of 6.8 years and 26 were adults (66.7%) with a mean age of 36.3 years. The location of hydatid cysts was intracranial in 27 cases (69.2%) and spinal in 12 cases (30.8%). Headache and motor deficits were the predominant symptoms in patients with intracranial hydatidosis whereas back pain and spinal cord compression syndrome were the most frequent clinical presentations in patients with spinal hydatidosis. All patients underwent surgical resection of the cyst. Pathologic findings were consistent with hydatid cyst in all cases. During the follow-up period which ranged between 12 months and 5 years, 12 patients had recurrence (30.7%). Only one patient with intracranial hydatid cyst died postoperatively due to anaphylactic shock.Conclusion
Despite all the advances in imaging techniques and therapeutic methods, central nervous system hydatidosis remains difficult to cure and patient outcomes are not satisfactory especially in case of spinal involvement due to the high incidence of recurrence. 相似文献87.
88.
In controlled clinical trials, where minimizing treatment failures is crucial, response-adaptive designs are attractive competitors to 1:1 randomized designs for comparing the success rates φ(1) and φ(2) of two treatments. In these designs each new treatment assignment depends on previous outcomes through some predefined rule. Here Play-The-Winner (PW), Randomized Play-The-Winner (RPW), Drop-The-Loser, Generalized Drop-the-Loser and Doubly adaptive Biased Coin Designs are considered for new treatment assignments. As frequentist inference relies on complex sampling distributions in those designs, we investigate how Bayesian inference, based on two independent Beta prior distributions, performs from a frequentist point-of-view. Performance is assessed through coverage probabilities of interval estimation procedures, power and minimization of failure count. It is shown that Bayesian inference can be favorably compared to frequentist procedures where the latter are available. The power of response-adaptive designs is generally very close to the power of 1:1 randomized design. However, failure count savings are generally small, except for the PW and Doubly adaptive Biased Coin designs in particular ranges of the true success rates. The RPW assignment rule has the worst performance, while PW, Generalized Drop-the-Loser or Doubly adaptive Biased Coin Designs may outperform other designs depending on different particular ranges of the true success rates. 相似文献
89.
Liu D Chan SL de Souza-Pinto NC Slevin JR Wersto RP Zhan M Mustafa K de Cabo R Mattson MP 《Neuromolecular medicine》2006,8(3):389-413
The high-metabolic demand of neurons and their reliance on glucose as an energy source places them atrisk for dysfunction
and death under conditions of metabolic and oxidative stress. Uncoupling proteins (UCPs) are mitochodrial inner membrane proteins
implicated in the regulation of mitochondrial membrane potential (ΔΨm) and cellular energy metabolism. The authors cloned UCP4 cDNA from mouse and rat brain, and demonstrate that UCP4 mRNA is
expressed abundantly in brain and at particularly high levels in populations of neurons believed to have high-energy requirements.
Neural cells with increased levels of UCP4 exhibit decreased ΔΨm, reduced reactive oxygen species (ROS) production and decreased mitochondrial calcium accumulation. UCP4 expressing cells
also exhibited changes of oxygen-consumption rate, GDP sensitivity, and response of ΔΨm to oligomycin that were consistent with mitochondrial uncoupling. UCP4 modulates neuronal energy metabolism by increasing
glucose uptake and shifting the mode of ATP production from mitochodnrial respiration to glycolysis, thereby maintaining cellular
ATP levels. The UCP4-mediated shift in energy metabolism reduces ROS production and increases the resistance of neurons to
oxidative and mitochondrial stress. Knockdown of UCP4 expression by RNA interference in primary hippocampal neurons results
in mitochondrial calcium overload and cell death. UCP4-mRNA expression is increased in neurons exposed to cold temperatures
and in brain cells of rats maintained on caloric restriction, suggesting a role for UCP4 in the previously reported antiageing
and neuroprotective effects of caloric restriction. By shifting energy metabolism to reduce ROS production and cellular reliance
on mitochondrial respiration, UCP4 can protect neurons against oxidative stress and calcium overload.
These authors made equal contributions to this research. 相似文献
90.
Yousri El Kissi Asma Ben Romdhane Samir Hidar Souhail Bannour Khadija Ayoubi Idrissi Hedi Khairi Bechir Ben Hadj Ali 《European journal of obstetrics, gynecology, and reproductive biology》2013