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Biere-Rafi S Di Nisio M Gerdes V Porreca E Souverein P Boer A Büller H Kamphuisen P 《Pharmacoepidemiology and drug safety》2011,20(6):635-642
Purpose Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been associated with an increased risk of arterial thrombosis, but their effect on venous thrombotic events is less well established. The study aimed to assess the risk of symptomatic pulmonary embolism (PE) in patients using NSAIDs and to evaluate any effect of type, dose, and duration of therapy. Methods A case–control study was conducted using the PHARMO Record Linkage System, a Dutch population‐based registry. Cases were patients hospitalized with a primary diagnosis of PE and were matched to controls without a history of PE. To exclude confounding by indication, the effect of painkillers without known hemostatic effects was assessed. Results The study population consisted of 4433 cases and 16 802 controls. After adjustment for surgery, trauma, and malignancy, current use of NSAIDs was associated with PE (odds ratio (OR) 2.39, 95% confidence interval (CI) 2.06–2.77). The risk was highest for traditional NSAIDs, and the overall risk for NSAIDs was highest in the first 30 days of exposure (OR 4.77, 95%CI 3.92–5.81), as compared with chronic (<1 year; OR 1.83, 95%CI 1.47–2.28) or long‐term use (>1 year; OR 2.14, 95%CI 1.48–3.09). Use of acetaminophen and tramadol also increased the risk of PE (OR 1.74, 95%CI 1.42–2.14 and OR 4.07, 95%CI 2.86–5.75, respectively) with a similar time trend. Conclusions Use of NSAIDs is associated with an increased risk of symptomatic PE. This association may be partially explained by underlying medical conditions, as suggested by a similarly increased thrombotic risk in patients receiving acetaminophen and tramadol. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
995.
Anzini M Valenti S Braile C Cappelli A Vomero S Alcaro S Ortuso F Marinelli L Limongelli V Novellino E Betti L Giannaccini G Lucacchini A Daniele S Martini C Ghelardini C Di Cesare Mannelli L Giorgi G Mascia MP Biggio G 《Journal of medicinal chemistry》2011,54(16):5694-5711
3-Substituted 6-phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and related compounds were synthesized as central benzodiazepine receptor (CBR) ligands. Most of the compounds showed high affinity for bovine and human CBR, their K(i) values spanning from the low nanomolar to the submicromolar range. In particular, imidazoester 5f was able to promote a massive flow of (36)Cl(-) in rat cerebrocortical synaptoneurosomes overlapping its efficacy profile with that of a typical full agonist. Compound 5f was then examined in mice for its pharmacological effects where it proved to be a safe anxiolytic agent devoid of the unpleasant myorelaxant and amnesic effects of the classical 1,4-benzodiazepines. Moreover, the selectivity of some selected compounds has been assessed in recombinant α(1)β(2)γ(2)L, α(2)β(1)γ(2)L, and α(5)β(2)γ(2)L human GABA(A) receptors. Finally, some compounds were submitted to molecular docking calculations along with molecular dynamics simulations in the Cromer's GABA(A) homology model. 相似文献
996.
Butini S Gemma S Brindisi M Borrelli G Lossani A Ponte AM Torti A Maga G Marinelli L La Pietra V Fiorini I Lamponi S Campiani G Zisterer DM Nathwani SM Sartini S La Motta C Da Settimo F Novellino E Focher F 《Journal of medicinal chemistry》2011,54(5):1401-1420
Adenosine kinase (AK) catalyzes the phosphorylation of adenosine (Ado) to AMP by means of a kinetic mechanism in which the two substrates Ado and ATP bind the enzyme in a binary and/or ternary complex, with distinct protein conformations. Most of the described inhibitors have Ado-like structural motifs and are nonselective, and some of them (e.g., the tubercidine-like ligands) are characterized by a toxic profile. We have cloned and expressed human AK (hAK) and searched for novel non-substrate-like inhibitors. Our efforts to widen the structural diversity of AK inhibitors led to the identification of novel non-nucleoside, noncompetitive allosteric modulators characterized by a unique molecular scaffold. Among the pyrrolobenzoxa(thia)zepinones (4a-qq) developed, 4a was identified as a non-nucleoside prototype hAK inhibitor. 4a has proapoptotic efficacy, slight inhibition of short-term RNA synthesis, and cytostatic activity on tumor cell lines while showing low cytotoxicity and no significant adverse effects on short-term DNA synthesis in cells. 相似文献
997.
Gemma S Kunjir S Coccone SS Brindisi M Moretti V Brogi S Novellino E Basilico N Parapini S Taramelli D Campiani G Butini S 《Journal of medicinal chemistry》2011,54(16):5949-5953
Here we report the synthesis and evaluation of antiplasmodial activity of a novel series of bicyclic peroxides inspired by the marine natural compound dihydroplakortin. We developed a synthetic strategy leading to the dihydroplakortin-related peroxides in only a few steps. The in vitro antiplasmodial potency of the peroxides was similar to, or greater than, that of the reference natural compound, and structure-activity relationship studies revealed several key structural requirements for activity and potency. 相似文献
998.
Luciano Chaves Arantes Ettore Ferrari Júnior Luciano Figueiredo de Souza Andriele Costa Cardoso Thaynara Lino Fernandes Alcântara Luciano Morais Lião Yuri Machado Rogério Araújo Lordeiro José Coelho Neto Ana Flávia B. Andrade 《Forensic Toxicology》2017,35(2):408-414
A new potent serotonin 5-HT2A receptor agonist was identified in blotter papers by several state level forensic laboratories in Brazil. The 25I-NBOH is a labile molecule, which fragments into 2C-I when analyzed by routine seized material screening gas chromatography (GC) methods. GC–mass spectrometry (MS), liquid chromatography–quadrupole time-of-flight-MS, and Fourier transform infrared and nuclear magnetic resonance analyses were performed to complete molecular characterization. Individual doses range from 300 to 1000 μg. Despite its being a potent 5-HT2A receptor agonist, 25I-NBOH is neither registered in the United Nations Office on Drugs and Crime (UNODC) nor classified as a scheduled substance in most countries. Sweden and Brazil seem to be the only countries to control 25I-NBOH. To our knowledge, this is the first scientific report dealing with identification of 25I-NBOH in actual seizures. 相似文献
999.
The most difficult aspect regarding treatment of the pediatric flatfoot is understanding who needs surgery,when it is necessary, and what procedure to be done.A thorough history, clinical examination, and imaging should be performed to guide the surgeon through an often complex treatment path. Surgical technique can be divided in three categories: Soft tissue, bony,and arthroereisis. This paper will describe the jointpreserving techniques and their application to treat the pediatric flatfoot deformity. 相似文献
1000.
Mario Commodo Gianluigi De Falco Ettore Sarnelli Marcello Campajola Alberto Aloisio Andrea DAnna Patrizia Minutolo 《Materials》2021,14(16)
Nanostructured films of carbon and TiO2 nanoparticles have been produced by means of a simple two-step procedure based on flame synthesis and thermophoretic deposition. At first, a granular carbon film is produced on silicon substrates by the self-assembling of thermophoretically sampled carbon nanoparticles (CNPs) with diameters of the order of 15 nm. Then, the composite film is obtained by the subsequent thermophoretic deposition of smaller TiO2 nanoparticles (diameters of the order of 2.5 nm), which deposit on the surface and intercalate between the carbon grains by diffusion within the pores. A bipolar resistive switching behavior is observed in the composite film of CNP-TiO2. A pinched hysteresis loop is measured with SET and RESET between low resistance and high resistance states occurring for the electric field of 1.35 × 104 V/cm and 1.5 × 104 V/cm, respectively. CNP-TiO2 film produced by flame synthesis is initially in the low resistive state and it does not require an electroforming step. The resistance switching phenomenon is attributed to the formation/rupture of conductive filaments through space charge mechanism in the TiO2 nanoparticles, which facilitate/hinder the electrical conduction between carbon grains. Our findings demonstrate that films made of flame-formed CNP-TiO2 nanoparticles are promising candidates for resistive switching components. 相似文献