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排序方式: 共有832条查询结果,搜索用时 15 毫秒
1.
Emeline Colomba Patricia Pautier Fanny Pommeret Alexandra Leary 《Expert review of anticancer therapy》2019,19(6):437-446
Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.
Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.
Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited. 相似文献
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Pelosi G Scarpa A Veronesi G Spaggiari L Del Curto B Moore PS Maisonneuve P Sonzogni A Masullo M Viale G 《Virchows Archiv : an international journal of pathology》2005,447(6):969-977
Nuclear translocation of β-catenin has been correlated with epidermal growth factor receptor (EGFR) overexpression/activation
in nonsmall cell lung cancer. Less is known on β-catenin transactivation in high-grade pulmonary neuroendocrine tumors and
on the status of β-catenin activating EGFR and human epidermal growth factor receptor 2 (HER-2) or β-catenin target genes
cyclin D1 and matrix metalloproteinase-7 (MMP-7). β-catenin immunoreactivity was evaluated in 51 large-cell neuroendocrine
carcinomas (LCNEC) and 45 small-cell lung carcinomas (SCLC). Nineteen cases were assessed for β-catenin gene exon 3 mutations, expression of MMP-7, and expression/gene amplification of EGFR, HER-2, and cyclin D1. β-catenin was
expressed in all 96 high-grade neuroendocrine tumors, the vast majority (94%) showing >50% immunopositive cells. A disarrayed
immunoreactivity, however, was commonly encountered consisting in variably altered membrane-associated patterns of staining
along with progressive accumulation of cytoplasmic immunoreactivity. In LCNEC, but not in SCLC, the disarrayed patterns correlated
with EGFR and HER-2 protein expression. β-catenin nuclear accumulation was found in nine tumors, including seven LCNEC and
two SCLC, and was always associated with disarrayed immunoreactivity and increased MMP-7, but not cyclin D1 expression. These
cases, however, did not show β-catenin gene mutations or EGFR and HER-2 gene amplification or expression. No association was found between nuclear β-catenin and
any clinicopathological variable including patients' survival. The subcellular compartmentalization of β-catenin is profoundly
altered in high-grade pulmonary neuroendocrine tumors. A minor subset of these tumors shows β-catenin nuclear accumulation
in association with increased expression of MMP-7, but not of cyclin D1, independent of EGFR and HER-2 gene amplification
or expression.
The authors have no significant financial or other relationship with the manufacturers of any commercial products or commercial
services presented in this paper 相似文献
3.
Ken Dewitte Marc Claeys Emeline Van Craenenbroeck Koen Monsieurs Hein Heidbuchel Vicky Hoymans Tibor Stoop 《Pathophysiology》2019,26(1):53-59
Aims
We explored the effect of remote ischaemic conditioning (RIC) on endothelial function and on circulating mediators.Methods and results
In 20 healthy male volunteers (mean age 31?±?10 years), flow-mediated dilation (FMD) was measured before and after 20?min of arm ischaemia, followed by reperfusion. Remote ischaemic conditioning (RIC) was performed by applying 3 cycles of 5?min of ischaemia of the leg at the onset of index arm ischaemia. Each volunteer underwent the IR-induced vascular injury protocol with and without RIC in a crossover study design.In the control group, IR significantly reduced FMD (5.9?±?2.9% before IR vs. 2.2?±?3.7% after IR; p?<?0.001). This effect was significantly attenuated by performing RIC (FMD of 5.5?±?3.1% before IR vs. 4.0?±?3.4% % after IR; p for interaction?=?0.01). Serum levels of SOD and ADMA increased significantly whereas MCP-1 and VEGF levels decreased significantly.Only changes in SOD levels were significantly related to the degree of RIC induced protection (r²?=?0.34; p?=?0.018).Conclusion
RIC has protective effects against endothelial IR injury. Our biomarker study suggests that anti-oxidative stress mediators, such as SOD, seem to be more involved in the pathogenesis of RIC-induced protection in humans than angiogenesis factors or chemo-attractant cytokines. 相似文献4.
K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung. 总被引:2,自引:0,他引:2
Giuseppe Pelosi Aldo Scarpa Michela Manzotti Giulia Veronesi Lorenzo Spaggiari Filippo Fraggetta Oscar Nappi Elvira Benini Felice Pasini Davide Antonello Antonio Iannucci Patrick Maisonneuve Giuseppe Viale 《Modern pathology》2004,17(5):538-546
We investigated 27 pleomorphic carcinomas of the lung for exon 1 K-ras gene mutations using polymerase chain reaction-single-strand conformation polymophism analysis and direct sequencing. All pleomorphic carcinomas were biphasic, that is, composed of an adeno-, squamous- or large-cell-carcinomatous component associated with a spindle- and/or giant-cell component. Of 27 cases, six (22%) showed K-ras codon 12 mutations, which is a figure higher than that previously reported on in pure sarcoma-like pleomorphic carcinomas. Five tumors displayed the same mutation in both the epithelial and the sarcomatoid components, whereas in one tumor the mutation was restricted to the epithelial component. All mutations occurred in smokers, and were transversions, including GGT (glycine) to TGT (cysteine) change in two cases, to GCT (alanine) in two and to GTT (valine) in two. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clinicopathological variable, suggesting that K-ras mutations are early events in the development of these tumors. Our results indicate that most, though not all, biphasic pleomorphic carcinomas of the lung are monoclonal in origin, and that cigarette smoking may have a causative role in the development of K-ras alterations in these tumors, as all mutations are transversions. 相似文献
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Rationale: Results of single-dose studies suggest that the effects of pretreatment with the putative anti-addictive compound, ibogaine,
on drug-induced locomotor behavior depends on the previous drug history of the animal. Objectives: To compare the effects of ibogaine pretreatment on the dose-locomotor response function for cocaine in rats treated chronically
with either saline or cocaine. Methods: Rats were chronically treated with either cocaine (15 mg/kg, IP, once daily for 5 days, followed by 2 week withdrawal) or
saline. Ibogaine (40 mg/kg, IP) or vehicle was administered and 19 h later, a cocaine dose-locomotor response test was conducted
(0, 5, 10, 20 and 40 mg/kg, IP). Results: Chronic cocaine administration augmented the locomotor response to cocaine in chronic cocaine-treated rats, compared to
acutely treated controls. Ibogaine pretreatment enhanced the locomotor effects of cocaine in both chronic and acute cocaine
groups. Furthermore, due to the shape of the dose-response curve, in chronic cocaine but not in acute cocaine rats, ibogaine
pretreatment enhanced the locomotor response to 5 and 10 mg/kg cocaine while decreasing the locomotor response to 40 mg/kg
cocaine. Conclusions: These data demonstrate definitively that ibogaine can enhance sensitivity to the locomotor stimulant effects of cocaine,
an effect which depends, in part, on the previous cocaine history of the animal.
Received: 19 December 1998 / Final version: 2 March 1999 相似文献
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Massimo Bellomi Cristiano Rampinelli Giulia Veronesi Sergio Harari Federica Lanfranchi Sara Raimondi Patrick Maisonneuve 《European radiology》2010,20(2):286-292