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排序方式: 共有204条查询结果,搜索用时 140 毫秒
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Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献2.
Judit Gervai Zsofia Nemoda Krisztina Lakatos Zsolt Ronai Ildiko Toth Krisztina Ney Maria Sasvari-Szekely 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2005,(1):126-130
Following up the results of a previous population association study (Lakatos et al. [2000: Mol Psychiatry 5:633-637; Lakatos et al. [2002: Mol Psychiatry 7:27-31]) by analyses based on parental genetic data confirmed the link between infant attachment and the dopamine D4 receptor (DRD4) gene. Extended transmission disequilibrium tests (ETDT) were performed to determine whether biased transmission of exon III 48 basepair repeat alleles occurred to infants displaying disorganized and secure attachment behavior with their mothers. The overall allele-wise TDTs were significant for both groups (P = 0.038 and 0.020, respectively): a trend for preferential transmission of the seven-repeat allele to disorganized infants was observed (TDT(chi)(2) = 3.27, df = 1, P = 0.071), and there was a significant non-transmission of the same allele to securely attached infants (TDT(chi)(2) = 6.00, df = 1, P = 0.014). Analysis of haplotypes of the exon III repeat and the -521 C/T promoter polymorphisms in family trios showed that the transmission bias in the larger secure group was due to the low-rate transmission of the T.7 haplotype containing both the seven-repeat and the -521 T alleles (TDT(chi)(2) = 4.46, df = 1, P = 0.035). This suggests that not carrying the T.7 haplotype of the DRD4 gene may act as a resilience factor in the optimal development of early attachment. 相似文献
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Laura E. Brumariu Jean-François Bureau Zsofia Nemoda Maria Sasvari-Szekely Karlen Lyons-Ruth 《Journal of reproductive and infant psychology》2016,34(1):77-89
Objective: This study’s aim was to evaluate whether infant disorganised attachment and infant proneness to distress exhibited differential relations to infant genetic factors as indexed by the serotonin transporter polymorphism. Background: The role of the short allele of the serotonin transporter polymorphism (5-HTTLPR) in enhancing sensitivity to fearful and negative affect has been well-established. In the current study, we used this known property of the short allele to provide a test of an important postulate of attachment theory, namely that infant attachment security or disorganisation is not a function of the infant’s proneness to distress. Methods: Participants were 39 parents and infants assessed between 12 and 18 months in the Strange Situation Procedure. Genotype categories for the 5-HTTLPR (and rs25531) were created by both the original and the reclassified grouping system; infant proneness to distress was assessed directly in the Strange Situation Procedure. We also assessed maternal behaviour at 18 months to evaluate whether any observed genetic effect indicated a passive effect through the mother. Results: Consistent with previous findings, the 5-HTTLPR short allele was significantly related to the infant’s wariness and distress, but was not related to attachment security or attachment disorganisation. In addition, maternal disrupted interaction with the infant was not related to infant genotype or infant distress. Conclusion: Results support the concept that infant proneness to distress is associated with serotonergic factors while infant attachment security or disorganisation is not a function of either 5-HTTLPR or behaviourally rated proneness to distress. 相似文献
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Lenka Langhansova Premysl Landa Zsofia Kutil Jan Tauchen Petr Marsik Jan Rezek 《Food and Agricultural Immunology》2017,28(2):343-353
Myrica rubra Sieb. et Zucc. is a valuable fruit tree that is used in Chinese, Japanese and Taiwanese traditional medicine. We investigated the anti-inflammatory activity of M. rubra leaves extracted with four different solvents. Total phenolics were determined using the Folin–Ciocalteu method. Extracts were investigated for their inhibitory activity toward the pro-inflammatory enzymes cyclooxygenase-1 and -2 (COX-1, COX-2) and 5-lipoxygenase (5-LOX). The ethanol extract of M. rubra leaves demonstrated a strong inhibition of prostaglandin E2 (PGE2) biosynthesis catalyzed by both COX-1 (93.42%) and COX-2 (75.71%) and leukotriene B4 (LTB4) formation catalyzed by 5-LOX (82.72%). Further we identified selective COX-1 inhibition by the n-butanol and aqueous fractions of the ethanol extract (with an IC50 for COX-1 inhibition of 1.07 and 0.71?µg?mL?1 , respectively) and dual 5-LOX/COX inhibition by the ethyl acetate fraction (with an IC50 of 3.29 for COX-1, 2.54 for COX-2 and 8.30?µg?mL?1 for 5-LOX). 相似文献
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Circulating platelet-leukocyte hetero-aggregates play an important role in acute cardiovascular events and hypersensitivity reactions. The association involves the receptor families of selectins and integrin. The objective of this study was to investigate the role of CD11b/CD18 integrin (Mac-1) in hetero-aggregate formation and search for a counter-receptor on platelets ready to interact with Mac-1. As a model of leukocytes, Mac-1 presenting Chinese hamster ovary (CHO) cells were used to evaluate the role of Mac-1 in hetero-aggregate formation. The amount of CHO cell-bound active and inactive platelets was measured by flow cytometry, while the counter-receptors on platelets were identified via using blocking antibodies. We observed significant platelet adhesion on Mac-1-bearing cells when platelet-rich plasma or activated platelets were present. Inactive platelets did not adhere to Mac-1-bearing cells. Addition of fibrinogen, a ligand of Mac-1 significantly increased platelet binding. CD40L was demonstrated to act similarly on Mac-1. Inhibition of platelet GpIIb/IIIa completely abolished CHO cell-platelet aggregation. In our study, we have shown for the first time that Mac-1 mediates the formation of hetero-aggregates without selectin tethering when Mac-1 ligands such as fibrinogen or CD40L are present and blockers of platelet GpIIb/IIIa are able to diminish this interaction. 相似文献
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Katalin Gulyas Nora Bodnar Zsofia Nagy Szilvia Szamosi Agnes Horvath Andrea Vancsa Edit Vegh Zoltan Szabo Gabriella Szucs Zoltan Szekanecz Sandor Szanto 《The European journal of health economics》2014,15(1):93-112