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131.
132.
Stefania Momi Jessica Canino Mauro Vismara Luca Galgano Emanuela Falcinelli Giuseppe Guglielmini Giulia Ciarrocca Taranta Gianni Francesco Guidetti Paolo Gresele Mauro Torti Ilaria Canobbio 《Haematologica》2022,107(6):1374
Deep vein thrombosis results from the cooperative action of leukocytes, platelets, and endothelial cells. The proline-rich tyrosine kinase Pyk2 regulates platelet activation and supports arterial thrombosis. In this study, we combined pharmacological and genetic approaches to unravel the role of Pyk2 in venous thrombosis. We found that mice lacking Pyk2 almost completely failed to develop deep venous thrombi upon partial ligation of the inferior vena cava. Pyk2-deficient platelets displayed impaired exposure of phosphatidylserine and tissue factor expression by endothelial cells and monocytes was completely prevented by inhibition of Pyk2. In human umbilical vein endothelial cells (HUVEC), inhibition of Pyk2 hampered IL-1β-induced expression of VCAM and P-selectin, and von Willebrand factor release. Pyk2-deficient platelets showed defective adhesion on von Willebrand factor and reduced ability to bind activated HUVEC under flow. Moreover, inhibition of Pyk2 in HUVEC strongly reduced platelet adhesion. Similarly, Pyk2-deficient neutrophils were unable to efficiently roll and adhere to immobilized endothelial cells under venous flow conditions. Moreover, platelets and neutrophils from Pyk2-knockout mice showed defective ability to form heterogeneous aggregates upon stimulation, while platelet monocyte interaction occurred normally. Consequently, platelet neutrophil aggregates, abundant in blood of wild-type mice upon inferior vena cava ligation, were virtually undetectable in Pyk2-knockout mice. Finally, we found that expression of Pyk2 was required for NETosis induced by activated platelets. Altogether our results demonstrate a critical role of Pyk2 in the regulation of the coordinated thromboinflammatory responses of endothelial cells, leukocytes and platelets leading to venous thrombosis. Pyk2 may represent a novel promising target in the treatment of deep vein thrombosis. 相似文献
133.
Priscilla R. V. Campana Daniel S. Mansur Grasielle S. Gusman Daneel Ferreira Mauro M. Teixeira Fernão C. Braga 《Phytotherapy research : PTR》2015,29(10):1509-1515
Several plant species are used in Brazil to treat inflammatory diseases and associated conditions. TNF‐α plays a pivotal role on inflammation, and several plant extracts have been assayed against this target, both in vitro and in vivo. The effect of 11 Brazilian medicinal plants on TNF‐α release by LPS‐activated THP‐1 cells was evaluated. The plant materials were percolated with different solvents to afford 15 crude extracts, whose effect on TNF‐α release was determined by ELISA. Among the evaluated extracts, only Jacaranda caroba (Bignoniaceae) presented strong toxicity to THP‐1 cells. Considering the 14 non‐toxic extracts, TNF‐α release was significantly reduced by seven of them (inhibition > 80%), originating from six plants, namely Cuphea carthagenensis (Lythraceae), Echinodorus grandiflorus (Alismataceae), Mansoa hirsuta (Bignoniaceae), Ouratea semiserrata (Ochnaceae), Ouratea spectabilis and Remijia ferruginea (Rubiaceae). The ethanol extract from O. semiserrata leaves was fractionated over Sephadex LH‐20 and RP‐HPLC to give three compounds previously reported for the species, along with agathisflavone and epicatechin, here described for the first time in the plant. Epicatechin and lanceoloside A elicited significant inhibition of TNF‐α release, indicating that they may account for the effect produced by O. semiserrata crude extract. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
134.
Transient elastography for non‐invasive evaluation of post‐transplant liver graft fibrosis in children 下载免费PDF全文
Tiziana Vinciguerra Andrea Brunati Ezio David Filomena Longo Michele Pinon Fulvio Ricceri Luisa Castellino Antonio Piga Maria Teresa Giraudo Francesco Tandoi Fabio Cisarò Dominic Dell Olio Giuseppe Isolato Renato Romagnoli Mauro Salizzoni Pier Luigi Calvo 《Pediatric transplantation》2018,22(2)
As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow‐up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non‐invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non‐invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100‐fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval ‐0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non‐invasive, reliable tool for the assessment of graft fibrosis in the follow‐up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies. 相似文献
135.
Andrs Villaseor Espinosa Danilo de Souza Costa Luiza Guimares Tunes Rubens L. do Monte‐Neto Richard Michael Grazul Mauro Vieira de Almeida Heveline Silva 《Chemical biology & drug design》2021,97(1):41-50
Four gold(I) complexes conceived as anticancer agents were synthesized by reacting [Au(PEt3)Cl] and [Au(PPh3)Cl] with ligands derived from δ‐d ‐gluconolactone. The ligands’ structure was designed to combine desired biological properties previously reported for each group. Ligands were synthesized from δ‐d ‐gluconolactone via ketal protection and hydrazide formation followed by cyclization with CS2 to produce the novel oxadiazolidine‐2‐thione 7 and 8 . Increasing of the ligands’ lipophilicity via ketal protection proved useful since all four gold(I) complexes showed anticancer and antileishmanial properties. The IC50 values are at low micromolar range, varying from 2 to 3 μm for the most active compounds. The free D‐gluconate 1,3,4 oxadiazole‐derived ligands were neither toxic nor presented anticancer or antileishmanial properties. Triethylphosphine‐derived compounds 9 and 10 were more selective against B16‐F10 melanoma cell line. Although similar in vitro antileishmanial activity was observed for the gold(I) precursors themselves and their derived complexes, the latter were three times less toxic for human THP‐1 macrophage cell line; this result is attributed to an isomeric variation of the D‐gluconate ligand and the oxadiazole portion, which was one of the key concepts behind this work. These findings should encourage further research on gold(I) complexes to develop novel compounds with potential application in cancer and leishmaniasis chemotherapy. 相似文献
136.
Roberta Cassano Teresa Ferrarelli Maria Vittoria Mauro Paolina Cavalcanti Nevio Picci 《Drug delivery》2016,23(3):1037-1046
The present article reports the preparation, characterization and performance evaluation of solid lipid nanoparticles (SLNs) based on polyoxyethylene-40 stearate (PEG-40 stearate) for the administration of antifungal agents such as ketoconazole and clotrimazole. These nanoparticles could be useful in the treatment of vaginal infections sustained by Candida albicans. In particular, PEG-40 stearate was made to react with acryloyl chloride in order to introduce an easily polymerizable moiety for the creation of a second shell and to ensure a slow drug release. In addition, the differences on the release profiles between PEG-40 stearate-based nanoparticles, PEG-40 stearate acrylate based and polymerized ones, were analyzed under conditions, simulating the typical environment of Candida albicans infection. Then, the antifungal activity of nanoparticles was also evaluated in terms of minimal inhibitory concentration. Moreover, the nanoparticles were submitted to in vitro studies for evaluating the drug permeability at the site of action. Results indicated that the obtained particles are potentially useful for the treatment of vaginal infections sustained by Candida albicans. 相似文献
137.
This paper reviews the state-of-the-art technologies, characterizations, materials (precursors and encapsulants), and challenges concerning multicolor and white light-emitting diodes (LEDs) based on carbon dots (CDs) as color converters. Herein, CDs are exploited to achieve emission in LEDs at wavelengths longer than the pump wavelength. White LEDs are typically obtained by pumping broad band visible-emitting CDs by an UV LED, or yellow–green-emitting CDs by a blue LED. The most important methods used to produce CDs, top-down and bottom-up, are described in detail, together with the process that allows one to embed the synthetized CDs on the surface of the pumping LEDs. Experimental results show that CDs are very promising ecofriendly candidates with the potential to replace phosphors in traditional color conversion LEDs. The future for these devices is bright, but several goals must still be achieved to reach full maturity. 相似文献
138.
139.
A small molecule Smac mimic potentiates TRAIL-mediated cell death of ovarian cancer cells 总被引:5,自引:0,他引:5
Petrucci E Pasquini L Petronelli A Saulle E Mariani G Riccioni R Biffoni M Ferretti G Benedetti-Panici P Cognetti F Scambia G Humphreys R Peschle C Testa U 《Gynecologic oncology》2007,105(2):481-492
OBJECTIVES: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (Smac) has been described to sensitize for apoptosis. We have explored the proapoptotic activity of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines (A2780 cells and its chemoresistant derivatives A2780/ADR and A2780/DDP), cancer cell lines and in primary ovarian cancer cells. METHODS: The effects of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines and primary ovarian cancer cells were determined by cell proliferation, apoptosis and biochemical assays. RESULTS: This compound added alone elicited only a weak proapoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAILR2 antibody (Lexatumumab) in inducing apoptosis of ovarian cancer cells. CONCLUSIONS: These observations suggest that small molecule mimic of Smac/DIABLO could be useful for the development of experimental strategies aiming to treat ovarian cancer. Interestingly, in addition to its well known proapoptotic effects, Smac/DIABLO elicited a significant increase of pro-caspase-3 levels. 相似文献
140.
Francesco Cogliati Dezza Alessandra Oliva Vera Mauro Francesco Eugenio Romani Raissa Aronica Giulia Savelloni Elena Casali Serena Valeri Francesca Cancelli Claudio Maria Mastroianni 《Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive》2022,30(2):211