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排序方式: 共有2109条查询结果,搜索用时 31 毫秒
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Sanne C. F. A. Huijberts Robin M. J. M. van Geel Emilie M. J. van Brummelen Frans L. Opdam Serena Marchetti Neeltje Steeghs Saskia Pulleman Bas Thijssen Hilde Rosing Kim Monkhorst Alwin D. R. Huitema Jos H. Beijnen Ren Bernards Jan H. M. Schellens 《Cancer chemotherapy and pharmacology》2020,85(5):917-930
KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated. 相似文献
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Matthew Malone Blaine G. Fritz Karen Vickery Saskia Schwarzer Varun Sharma Nathan Biggs Michael Radzieta Thomas T. Jeffries Hugh G. Dickson Slade O. Jensen Thomas Bjarnsholt 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2019,127(10):660-670
Multiple approaches were employed to detect pathogens from bone margins associated with Diabetic Foot Osteomyelitis (DFO). Intra‐operative bone specimens of 14 consecutive subjects with suspected DFO were collected over a six‐month study period from Liverpool Hospital. Infected bone and a proximal bone margins presumed to be ‘clean/non‐infected’ were collected. Bone material was subjected to conventional culture, DNA sequencing and microscopy. In total, eight of 14 (57%) proximal bone margins had no growth by conventional culture but were identified in all proximal bone specimens by DNA sequencing. Proximal margins had lower median total microbial counts than infected specimens, but these differences were not statistically significant. Pathogens identified by sequencing in infected specimens were identified in proximal margins and the microbiomes were similar (ANOSIM = 0.02, p = 0.59). Using a combination of SEM and/or PNA‐FISH, we visualized the presence of microorganisms in infected bone specimens and their corresponding proximal margins of seven patients (50%) with DFO. We identify that bacteria can still reside in what seems to be proximal ‘clean’ margins. The significance and implications of clinical outcomes requires further analysis from a larger sample size that incorporates differences in surgical and post‐operative approaches, correlating any outcomes back to culture‐sequence findings. 相似文献
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Martin Liebl Federico Pedersoli Markus Zimmermann Maximilian Schulze-Hagen Daniel Truhn Paul Sieben Saskia von Stillfried Anna Tschinaev Alexander Heinzel Christiane K. Kuhl Philipp Bruners Peter Isfort 《Journal of vascular and interventional radiology : JVIR》2021,32(6):836-842.e2
PurposeTo compare hepatic hypertrophy in the contralateral lobe achieved by unilobar transarterial radioembolization (TARE) versus portal vein embolization (PVE) in a swine model.MethodsAfter an escalation study to determine the optimum dose to achieve hypertrophy after unilobar TARE in 4 animals, 16 pigs were treated by TARE (yttrium-90 resin microspheres) or PVE (lipiodol/n-butyl cyanoacrylate). Liver volume was calculated based on CT before treatment and during 6 months of follow-up. Independent t-test (P < .05) was used to compare hypertrophy. The relationship between hypertrophy after TARE and absorbed dose was calculated using the Pearson correlation.ResultsAt 2 and 4 weeks after treatment, a significantly higher degree of future liver remnant hypertrophy was observed in the PVE group versus the TARE group, with a median volume gain of 31% (interquartile range [IQR]: 16%–66%) for PVE versus 23% (IQR: 6%–36%) for TARE after 2 weeks and 51% (IQR: 47%–69%) for PVE versus 29% (IQR: 20%–50%) for TARE after 4 weeks. After 3 and 6 months, hypertrophy converged without a statistically significant difference, with a volume gain of 103% (IQR: 86%–119%) for PVE versus 82% (IQR: 70%–96%) for TARE after 3 months and 115% (IQR: 70%–46%) for PVE versus 86% (IQR: 58%–111%) for TARE after 6 months. A strong correlation was observed between radiation dose (median 162 Gy, IQR: 139–175) and hypertrophy.ConclusionsPVE resulted in rapid hypertrophy within 1 month of the procedure, followed by a plateau, whereas TARE resulted in comparable hypertrophy by 3–6 months. TARE-induced hypertrophy correlated with radiation absorbed dose. 相似文献
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Tim Both Virgil A.S.H. Dalm Savannah A. Richardson Naïma van Schie Luuk M. van den Broek Annemarie C. de Vries P. Martin van Hagen Saskia M. Rombach 《Autoimmunity reviews》2021,20(8):102872
ObjectiveTo describe the prevalence, clinical presentation and current treatment regimens of inflammatory bowel disease (IBD) in patients with primary immunodeficiency disorders (PIDs).MethodsA systematic review was conducted. The following databases were searched: MEDLINE, Embase, Web of Science, the Cochrane Library and Google Scholar.ResultsA total of 838 articles were identified, of which 36 were included in this review. The prevalence of IBD in PIDs ranges between 3.4% and 61.2%, depending on the underlying PID. Diarrhea and abdominal pain were reported in 64.3% and 52.4% of the patients, respectively. Colon ulceration was the most frequent finding on endoscopic evaluation, while cryptitis, granulomas, ulcerations and neutrophilic/lymphocytic infiltrates were the most frequently reported histopathological abnormalities. Described treatment regimens included oral corticosteroids and other oral immunosuppressive agents, including mesalazine, azathioprine and cyclosporin, leading to clinical improvement in the majority of patients. In case of treatment failure, biological therapies including TNF- α blocking agents, are considered.ConclusionsThe overall prevalence of IBD in patients with PID is high, but varies between different PIDs. Physicians should be aware of these complications and focus on characteristic symptoms to reduce diagnostic delay and delay in initiation of treatment. Treatment of IBD in PIDs depends on severity of symptoms and may differ between various PIDs based on distinct underlying pathogenesis. An individualized diagnostic and therapeutic approach is therefore warranted. 相似文献
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Factors Associated with Reported Infection and Lymphedema Symptoms among Individuals with Extremity Lymphedema 下载免费PDF全文
Jie Deng PhD RN OCN Mei R. Fu PhD RN APRN‐BC FAAN Jane M. Armer PhD RN FAAN Janice N. Cormier MD MPH M. Elise Radina PhD CFLE Saskia R.J. Thiadens RN Jan Weiss PT DHS CLT‐LANA Catherine M. Tuppo PT MS CLT‐LANA Mary S. Dietrich PhD Sheila H. Ridner PhD RN FAAN 《Rehabilitation nursing》2015,40(5):310-319
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Anita van de Munckhof Katarzyna Krzywicka Diana Aguiar de Sousa Mayte Snchez van Kammen Mirjam R. Heldner Katarina Jood Erik Lindgren Turgut Tatlisumak Jukka Putaala Johanna A. Kremer Hovinga Saskia Middeldorp Marcel Levi Marcel Arnold Jos M. Ferro Jonathan M. Coutinho 《European journal of neurology》2022,29(1):339-344