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61.
Diamantis I. Tsilimigras Ioannis Ntanasis-Stathopoulos Fabio Bagante Demetrios Moris Jordan Cloyd Eleftherios Spartalis Timothy M. Pawlik 《Surgical oncology》2018,27(2):280-288
Background
Hepatic resection is considered the optimal potentially curative treatment for colorectal liver metastases (CRLM). Following resection, up to two-thirds of patients will develop recurrence within 5-years. Genetic mutation analysis of CRLM, especially KRAS status, has been proposed as a means to guide treatment, as well as identifying patients who can derive the most survival benefit from hepatic resection.Methods
A systematic review of the literature was conducted the PubMed, Embase and Cochrane library through February 8th, 2018. The following algorithm was applied: “(colorectal OR rectal OR colon OR colonic) AND (liver OR hepatic) AND (metastasis OR metastases) AND (gene OR mutation OR KRAS OR BRAF OR SMAD4 OR RAS OR TP53 OR P53 OR APC OR PI3K OR MSI OR EGFR OR MACC1 OR microsatellite).”Results
From the 2404 records retrieved, 78 studies were finally deemed eligible; 47 studies reported mutational data on patients with resectable CRLM, whereas 31 studies reported on patients with unresectable CRLM. Mutational analyses were mostly performed on the CRLM specimen rather than the primary CRC. The vast majority of studies reported on the KRAS mutational status (88.5%, n?=?69/78). Prevalence of KRAS mutations ranged from 25% to 52%. Most studies reported that RAS mutation was a negative prognostic factor for overall (OS) (n?=?24) and recurrence-free (RFS) (n?=?9) survival; a few reports noted no effect of RAS mutational status on OS (n?=?4) or RFS (n?=?6). Twelve studies reported on BRAF mutations with a prevalence of BRAF mutation ranging from 0 to 9.1% in resected CRLM specimens. BRAF mutation was strongly associated with a worse prognosis. TP53 and PIK3CA gene mutations did not affect long-term outcomes.Conclusions
The biological status of each tumor provides the basis for individualized cancer therapeutics. Data on the mutational status on CRLM should be a part of multidisciplinary discussions to help inform the therapeutic approach, type of chemotherapy, as well as timing and approach of surgical resection. 相似文献62.
N Chand J Pillar K Nolan W Diamantis R D Sofia 《International archives of allergy and applied immunology》1990,92(2):143-147
Azelastine produced a concentration-dependent inhibition of calcium ionophore A23187 (0.2 microM) stimulated generation of 5-HETE, leukotriene B4, and leukotriene C4 in rat mixed peritoneal cells, yielding IC50 values of 35.5, 47.4, and 31.7 microM, respectively. Nordihydroguaiaretic acid (a potent 5-lipoxygenase inhibitor) also exerted a strong and concentration-dependent inhibition of 5-HETE and leukotriene B4 and C4 formation with IC50 values of 0.15, 0.09, and 0.1 microM, respectively. The inhibition of the formation of the products of the lipoxygenase pathway of arachidonic acid metabolism by azelastine may contribute to its overall antiallergic, antiasthmatic, and pulmonary anti-inflammatory activities. 相似文献
63.
Inhibition of allergic and nonallergic leukotriene C4 formation and histamine secretion by azelastine: implication for its mechanism of action 总被引:1,自引:0,他引:1
N Chand J Pillar K Nolan W Diamantis R D Sofia 《International archives of allergy and applied immunology》1989,90(1):67-70
Azelastine, an orally effective antiasthmatic agent, has been reported to inhibit antihistamine-resistant, leukotriene-mediated allergic bronchoconstriction in guinea pigs. This suggests that azelastine might act through inhibition of leukotriene (LT) C4/D4 synthesis. We have examined the effect of azelastine on allergic and nonallergic histamine secretion and LTC4 formation. Azelastine and the known 5-lipoxygenase inhibitors, nordihydroguaiaretic acid and AA-861, exerted concentration-dependent inhibition of allergic LTC4 formation in chopped lung tissue from actively sensitized guinea pigs and calcium ionophore A23187-stimulated LTC4 synthesis in mixed peritoneal cells from rats. Azelastine also produced concentration-dependent inhibition of allergic and nonallergic histamine secretion from rat peritoneal mast cells. The ability of azelastine to inhibit allergic and nonallergic histamine secretion and LTC4 generation may contribute to its mode of action and its therapeutic efficacy. 相似文献
64.
Krki Tommi Plachouras Diamantis Cassini Alessandro Suetens Carl 《Wiener Medizinische Wochenschrift》2019,169(1):3-5
Wiener Medizinische Wochenschrift - Point prevalence surveys of healthcare-associated infections (HAI) and antimicrobial use in the European Union and European Economic Area (EU/EEA) from 2016 to... 相似文献
65.
Diamantis?I.?Tsilimigras Ioannis?Ntanasis-Stathopoulos Anargyros?Bakopoulos Dimitrios?Schizas Maria?Kalfa Irene?Karyda Dimitrios?Papaioannou Eirini?Klapsinou Charitini?Salla Theodoros?N.?SergentanisEmail author Maria?Moschovi 《Pediatric surgery international》2017,33(6):727-730
Intraductal papilloma (IP) constitutes a rare benign neoplasm among male population with only few reports on childhood patients. Herein, we describe an 11-year-old IP male patient who presented with spontaneous nipple discharge of his right breast. 相似文献
66.
Panagopoulos P Tsaganos T Plachouras D Carrer DP Papadopoulos A Giamarellou H Kanellakopoulou K 《International journal of antimicrobial agents》2008,32(6):485-487
Stimulan was evaluated in vitro as a biodegradable carrier for local delivery of moxifloxacin and fusidic acid. Moxifloxacin or fusidic acid was mixed with calcium sulphate at a ratio of 95:5 to prepare five replicas per antibiotic. In vitro elution was estimated daily using a high-performance liquid chromatography (HPLC) system. Elution of moxifloxacin lasted for 31 days. Eluted concentrations reached their peak on Day 13 (mean level 745 microg/mL); the lowest eluted concentration was detected on Day 30 (mean level 367 microg/mL). Elution of fusidic acid lasted for 14 days. Eluted concentrations reached their peak on Day 6 (mean value 249.5 microg/mL); the lowest eluted concentration was detected on Day 13 (mean value 10.9 microg/mL). The presented results revealed that Stimulan may allow adequate in vitro elution of moxifloxacin and fusidic acid. The latter results support the application of this system in experimental models of osteomyelitis. 相似文献
67.
George Mpekoulis Vassilina Tsopela Georgios Panos Vasilei¿s Siozos Katerina I. Kalliampakou Efseveia Frakolaki Constantinos D. Sideris Alice G. Vassiliou Diamantis C. Sideris Dido Vassilacopoulou Niki Vassilaki 《Viruses》2021,13(11)
A bidirectional negative relationship between Hepatitis C virus (HCV) replication and gene expression of the catecholamine biosynthetic enzyme L-Dopa decarboxylase (DDC) was previously shown in the liver and attributed at least to an association of DDC with phosphatidylinositol 3-kinase (PI3K). Here, we report that the biosynthesis and uptake of catecholamines restrict HCV replication in hepatocytes, while HCV has developed ways to reduce catecholamine production. By employing gene silencing, chemical inhibition or induction of the catecholamine biosynthetic and metabolic enzymes and transporters, and by applying the substrates or the products of the respective enzymes, we unravel the role of the different steps of the pathway in viral infection. We also provide evidence that the effect of catecholamines on HCV is strongly related with oxidative stress that is generated by their autoxidation in the cytosol, while antioxidants or treatments that lower cytosolic catecholamine levels positively affect the virus. To counteract the effect of catecholamines, HCV, apart from the already reported effects on DDC, causes the down-regulation of tyrosine hydroxylase that encodes the rate-limiting enzyme of catecholamine biosynthesis and suppresses dopamine beta-hydroxylase mRNA and protein amounts, while increasing the catecholamine degradation enzyme monoamine oxidase. Moreover, the NS4B viral protein is implicated in the effect of HCV on the ratio of the ~50 kDa DDC monomer and a ~120 kDa DDC complex, while the NS5A protein has a negative effect on total DDC protein levels. 相似文献
68.
Lu Wu MD Kota Sahara MD Diamantis I. Tsilimigras MD Shishir K. Maithel MD George A. Poultsides MD Flavio G. Rocha MD Sharon M. Weber MD Ryan C. Fields MD Kamran Idrees MD Clifford S. Cho MD Feng Shen MD Timothy M. Pawlik MD MPH PhD FACS and other members of the U.S. Neuroendocrine Tumor Study Group 《Journal of surgical oncology》2019,120(7):1080-1086
69.
70.
Sellis D Callahan BJ Petrov DA Messer PW 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(51):20666-20671
Molecular adaptation is typically assumed to proceed by sequential fixation of beneficial mutations. In diploids, this picture presupposes that for most adaptive mutations, the homozygotes have a higher fitness than the heterozygotes. Here, we show that contrary to this expectation, a substantial proportion of adaptive mutations should display heterozygote advantage. This feature of adaptation in diploids emerges naturally from the primary importance of the fitness of heterozygotes for the invasion of new adaptive mutations. We formalize this result in the framework of Fisher's influential geometric model of adaptation. We find that in diploids, adaptation should often proceed through a succession of short-lived balanced states that maintain substantially higher levels of phenotypic and fitness variation in the population compared with classic adaptive walks. In fast-changing environments, this variation produces a diversity advantage that allows diploids to remain better adapted compared with haploids despite the disadvantage associated with the presence of unfit homozygotes. The short-lived balanced states arising during adaptive walks should be mostly invisible to current scans for long-term balancing selection. Instead, they should leave signatures of incomplete selective sweeps, which do appear to be common in many species. Our results also raise the possibility that balancing selection, as a natural consequence of frequent adaptation, might play a more prominent role among the forces maintaining genetic variation than is commonly recognized. 相似文献