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41.
Papanikolaou IS Adler A Wegener K Al-Abadi H Dürr A Koch M Pohl H Abou-Rebyeh H Veltzke-Schlieker W Wiedenmann B Rösch T 《European journal of gastroenterology & hepatology》2008,20(4):342-348
OBJECTIVES: Endoscopic ultrasonography (EUS) with the adjunct of EUS-guided fine needle aspiration has become an important diagnostic modality in gastroenterologic oncology. EUS-guided fine needle aspiration mainly relies on cytology; data are scarce that compare cytology and histology. While testing a 22-gauge prototype needle, we prospectively compared the yield for both. METHODS: Forty-two consecutive patients (27 male, 15 female; mean age 59.2 years, range: 17-90 years) were included. In each patient we aimed to make two needle passes, and if the material acquired appeared insufficient macroscopically (no in-room cytopathology was available), further passes were done. The material was sent for cytological and histological assessment. RESULTS: A median number of two passes (range: 2-3) were uneventfully performed for pancreatic lesions (n=30), mediastinal and other lymph nodes/masses (n=8) and various other lesions (n=4) and yielded adequate material for cytology, histology or at least one of the two investigations in 62, 67 and 74% of patients, respectively. No false positive results were found (specificity 100%). Sensitivities were 58.6 and 65.5%, respectively, for cytology and histology alone; combined assessment increased sensitivity to 79.3%. When adjusted values were calculated, based only on those cases with adequate material, sensitivity was 89.5% for cytology and 85.7% for histology, and increased to 100% with combined assessment. CONCLUSION: The new needle achieves sensitivities similar to those previously reported with no significant differences in sensitivity between cytology and histology. More effective tissue acquisition methods must be sought to improve overall results. 相似文献
42.
A pro‐inflammatory signalome is constitutively activated by C33Y mutant TNF receptor 1 in TNF receptor‐associated periodic syndrome (TRAPS) 下载免费PDF全文
Ola H. Negm Heiko A. Mannsperger Elizabeth M. McDermott Elizabeth Drewe Richard J. Powell Ian Todd Lucy C. Fairclough Patrick J. Tighe 《European journal of immunology》2014,44(7):2096-2110
Mutations in TNFRSF1A encoding TNF receptor 1 (TNFR1) cause the autosomal dominant TNF receptor‐associated periodic syndrome (TRAPS): a systemic autoinflammatory disorder. Misfolding, intracellular aggregation, and ligand‐independent signaling by mutant TNFR1 are central to disease pathophysiology. Our aim was to understand the extent of signaling pathway perturbation in TRAPS. A prototypic mutant TNFR1 (C33Y), and wild‐type TNFR1 (WT), were expressed at near physiological levels in an SK‐Hep‐1 cell model. TNFR1‐associated signaling pathway intermediates were examined in this model, and in PBMCs from C33Y TRAPS patients and healthy controls. In C33Y‐TNFR1‐expressing SK‐Hep‐1 cells and TRAPS patients’ PBMCs, a subtle, constitutive upregulation of a wide spectrum of signaling intermediates and their phosphorylated forms was observed; these were associated with a proinflammatory/antiapoptotic phenotype. In TRAPS patients’ PBMCs, this upregulation of proinflammatory signaling pathways was observed irrespective of concurrent treatment with glucocorticoids, anakinra or etanercept, and the absence of overt clinical symptoms at the time that the blood samples were taken. This study reveals the pleiotropic effect of a TRAPS‐associated mutant form of TNFR1 on inflammatory signaling pathways (a proinflammatory signalome), which is consistent with the variable and limited efficacy of cytokine‐blocking therapies in TRAPS. It highlights new potential target pathways for therapeutic intervention. 相似文献
43.
Heiko Slanina Sabrina Mündlein Sabrina Hebling Alexandra Schubert-Unkmeir 《Infection and immunity》2014,82(3):1243-1255
Neisseria meningitidis, the causative agent of meningitis and septicemia, attaches to and invades various cell types. Both steps induce and/or require tyrosine phosphorylation of host cell proteins. Here, we used a phospho array platform to identify active receptor tyrosine kinases (RTKs) and key signaling nodes in N. meningitidis-infected brain endothelial cells to decipher RTK-dependent signaling pathways necessary for bacterial uptake. We detected several activated RTKs, including the ErbB family receptors epidermal growth factor receptor (EGFR), ErbB2, and ErbB4. We found that pharmacological inhibition and genetic ablation of ErbB receptor tyrosine phosphorylation and expression resulted in decreased bacterial uptake and heterologous expression of EGFR, ErbB2, or ErbB4 in Chinese ovary hamster (CHO-K1) cells, which do not express of EGFR and ErbB4; the decrease caused a significant increase in meningococcal invasion. Activation of EGFR and ErbB4 was mediated by transactivation via the common ligand HB-EGF (heparin-binding EGF-like ligand), which was significantly elevated in infected cell culture supernatants. We furthermore determined that N. meningitidis induced phosphorylation of EGFR at Tyr845 independent of ligand binding, which required c-Src activation and was involved in mediating uptake of N. meningitidis into eukaryotic cells. Increased uptake was repressed by expression of EGFR Y845F, which harbored a point mutation in the kinase domain. In addition, activation of ErbB4 at its autophosphorylation site, Tyr1284, and phosphorylation of ErbB2 Thr686 were observed. Altogether, our results provide evidence that EGFR, ErbB2, and ErbB4 are activated in response to N. meningitidis infection and shed new light on the role of ErbB signaling in meningococcal infection biology. 相似文献
44.
Elisabeth Salzer MD Aydan Kansu Heiko Sic Peter Májek Aydan Ikincioğullari Figen E. Dogu Nina Kathrin Prengemann Elisangela Santos-Valente Winfried F. Pickl Ivan Bilic Sol A BanZarife Kuloğlu MD Arzu Meltem Demir Arzu Ensari Jacques Colinge Marta Rizzi Hermann Eibel Kaan Boztug 《The Journal of allergy and clinical immunology》2014
45.
Heiko Sic Helene Kraus Josef Madl Karl-Andreas Flittner Audrey Lilly von Münchow Kathrin Pieper Marta Rizzi Anne-Kathrin Kienzler Korcan Ayata Sebastian Rauer Burkhard Kleuser Ulrich Salzer Meike Burger Katja Zirlik Vassilios Lougaris Alessandro Plebani Winfried Römer Christoph Loeffler Samantha Scaramuzza Anna Villa Emiko Noguchi Bodo Grimbacher Hermann Eibel 《The Journal of allergy and clinical immunology》2014
46.
Kathrin Pieper Marta Rizzi Matthaios Speletas Cristian R. Smulski Heiko Sic Helene Kraus Ulrich Salzer Gina J. Fiala Wolfgang W. Schamel Vassilios Lougaris Alessandro Plebani Lennart Hammarstrom Mike Recher Anastasios E. Germenis Bodo Grimbacher Klaus Warnatz Antonius G. Rolink Pascal Schneider Luigi D. Notarangelo Hermann Eibel 《The Journal of allergy and clinical immunology》2014
47.
Paige E. Cooper Heiko Reutter Joachim Woelfle Hartmut Engels Dorothy K. Grange Gijs van Haaften Bregje W. van Bon Alexander Hoischen Colin G. Nichols 《Human mutation》2014,35(7):809-813
ATP‐sensitive potassium (KATP) channels, composed of inward‐rectifying potassium channel subunits (Kir6.1 and Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and regulatory sulfonylurea receptor (SUR1 and SUR2, encoded by ABCC8 and ABCC9, respectively), couple metabolism to excitability in multiple tissues. Mutations in ABCC9 cause Cantú syndrome (CS), a distinct multiorgan disease, potentially via enhanced KATP channel activity. We screened KCNJ8 in an ABCC9 mutation‐negative patient who also exhibited clinical hallmarks of CS (hypertrichosis, macrosomia, macrocephaly, coarse facial appearance, cardiomegaly, and skeletal abnormalities). We identified a de novo missense mutation encoding Kir6.1[p.Cys176Ser] in the patient. Kir6.1[p.Cys176Ser] channels exhibited markedly higher activity than wild‐type channels, as a result of reduced ATP sensitivity, whether coexpressed with SUR1 or SUR2A subunits. Our results identify a novel causal gene in CS, but also demonstrate that the cardinal features of the disease result from gain of KATP channel function, not from a Kir6‐independent SUR2 function. 相似文献
48.
49.
Heiko Rühl Lars Schröder Jens Müller Rolf Fimmers Shorena Sukhitashvili Julia Welz Walther C. Kuhn Johannes Oldenburg Christian Rudlowski Bernd Pötzsch 《Thrombosis research》2014
Introduction
The estrogen antagonist tamoxifen (TAM) increases the thrombotic risk similar to estrogen containing oral contraceptives (OC). In OC users this risk is attributed to alterations of hemostasis resulting in acquired resistance to activated protein C (APC). TAM-induced APC resistance has not been reported yet.Materials and Methods
Blood samples were collected prospectively from women with breast cancer before (n = 25) and monthly after start of adjuvant TAM treatment (n = 75). APC resistance was evaluated on basis of the effect of APC on the endogenous thrombin generation potential. To detect increased in vivo APC generation APC plasma levels were measured using a highly sensitive oligonucleotide-based enzyme capture assay. Routine hemostasis parameters were measured additionally.Results
APC sensitivity decreased by 41% (p = 0.001) compared to baseline after one month of TAM application and remained significantly decreased during the study period. Free protein S increased (p = 0.008) while other analyzed procoagulant factors, inhibitors, and activation markers of coagulation decreased or did not change significantly. In five patients the APC concentration increased to non-physiological levels but an overall significant increase of APC was not observed.Conclusions
This is the first study showing acquired APC resistance under TAM therapy. Acquired APC resistance might explain the increased thrombotic risk during TAM treatment. Observed changes of hemostasis parameters suggest different determinants of TAM-induced APC resistance than in OC-induced APC resistance. The presence of acquired APC resistance in TAM patients warrants further evaluation if these patients may benefit from antithrombotic prophylaxis in the presence of additional thrombotic risk factors. 相似文献50.