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991.
BACKGROUND: Lipopolysaccharides (LPS), cleared from the blood by Kupffer cells, induce hypertriglyceridemia. AIMS: To test the hypothesis that GdCl(3), through inhibition of large Kupffer cell activity, modulates LPS-induced hyperlipidemia in rats. METHODS: Male Wistar rats received a single intravenous injection of GdCl(3)(10 mg/kg) or saline, 24 h before intraperitoneal LPS (1.5 mg/kg) administration. Serum and hepatic lipids as well as activity of key enzymes controlling fatty acid synthesis and esterification in liver tissue were measured. The incorporation of labeled precursors into lipids was assessed in cultured precision-cut liver slices. RESULTS: GdCl(3) does not prevent hypertriglyceridemia occurring in LPS-treated rats. Surprisingly, GdCl(3) per se is able to promote triglycerides accumulation in the liver tissue, an effect related to an increase in hepatic fatty acid esterification. Such an effect also occurs in rats receiving a dietary supplementation with glycine (5%) known to inhibit Kupffer cell secretory capacity. CONCLUSIONS: Large Kupffer cell inhibition does not prevent LPS-induced hypertriglyceridemia and even leads to a metabolic shift of fatty acids towards their esterification and accumulation in the liver tissue, suggesting that Kupffer cells play a role in the regulation of lipid metabolism of the adjacent hepatocytes, independent of any inflammatory stimulus. 相似文献
992.
993.
Anne-Claire Duchez Luc H. Boudreau Gajendra S. Naika James Bollinger Clémence Belleannée Nathalie Cloutier Benoit Laffont Raifish E. Mendoza-Villarroel Tania Lévesque Emmanuelle Rollet-Labelle Matthieu Rousseau Isabelle Allaeys Jacques J. Tremblay Patrice E. Poubelle Gérard Lambeau Marc Pouliot Patrick Provost Denis Soulet Michael H. Gelb Eric Boilard 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(27):E3564-E3573
994.
BRCA1 and BRCA2 Mutations in Ethnic Lebanese Arab Women With High Hereditary Risk Breast Cancer 下载免费PDF全文
Nagi S. El Saghir Nathalie K. Zgheib Hussein A. Assi Katia E. Khoury Yannick Bidet Sara M. Jaber Raghid N. Charara Rania A. Farhat Firas Y. Kreidieh Stephanie Decousus Pierre Romero Georges M. Nemer Ziad Salem Ali Shamseddine Arafat Tfayli Jaber Abbas Faek Jamali Muhieddine Seoud Deborah K. Armstrong Yves‐Jean Bignon Nancy Uhrhammer 《The oncologist》2015,20(4):357-364
Purpose.
Breast cancer is the most common malignancy among women in Lebanon and in Arab countries, with 50% of cases presenting before the age of 50 years.Methods.
Between 2009 and 2012, 250 Lebanese women with breast cancer who were considered to be at high risk of carrying BRCA1 or BRCA2 mutations because of presentation at young age and/or positive family history (FH) of breast or ovarian cancer were recruited. Clinical data were analyzed statistically. Coding exons and intron-exon boundaries of BRCA1 and BRCA2 were sequenced from peripheral blood DNA. All patients were tested for BRCA1 rearrangements using multiplex ligation-dependent probe amplification (MLPA). BRCA2 MLPA was done in selected cases.Results.
Overall, 14 of 250 patients (5.6%) carried a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) carried a variant of uncertain significance. Eight of 74 patients (10.8%) aged ≤40 years with positive FH and only 1 of 74 patients (1.4%) aged ≤40 years without FH had a mutated BRCA. Four of 75 patients (5.3%) aged 41–50 years with FH had a deleterious mutation. Only 1 of 27 patients aged >50 years at diagnosis had a BRCA mutation. All seven patients with BRCA1 mutations had grade 3 infiltrating ductal carcinoma and triple-negative breast cancer. Nine BRCA1 and 17 BRCA2 common haplotypes were observed.Conclusion.
Prevalence of deleterious BRCA mutations is lower than expected and does not support the hypothesis that BRCA mutations alone cause the observed high percentage of breast cancer in young women of Lebanese and Arab descent. Studies to search for other genetic mutations are recommended. 相似文献995.
Nathalie Quenel-Tueux Marc Debled Justine Rudewicz Gaetan MacGrogan Marina Pulido Louis Mauriac Florence Dalenc Thomas Bachelot Barbara Lortal Christelle Breton-Callu Nicolas Madranges Christine Tunon de Lara Marion Fournier Hervé Bonnefoi Hayssam Soueidan Macha Nikolski Audrey Gros Catherine Daly Henry Wood Pamela Rabbitts Richard Iggo 《British journal of cancer》2015,113(4):585-594
Background:
The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.Methods:
One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment.Results:
A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 53.8% (95% CI=39.5–67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0–71.9) in the anastrozole arm and 50.0% (95% CI=35.8–64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3–21.0) before, 3.2% (95% CI=1.9–5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1–22.5) before, 3.2% (95% CI=1.8–5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles.Conclusions:
Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients. 相似文献996.
Joffrey Pelletier Danièle Roux Benoit Viollet Nathalie M. Mazure Jacques Pouysségur 《Oncotarget》2015,6(14):11833-11847
Lactic acid generated by highly glycolytic tumours is exported by the MonoCarboxylate Transporters, MCT1 and MCT4, to maintain pHi and energy homeostasis. We report that MCT1 inhibition combined with Mct4 gene disruption severely reduced glycolysis and tumour growth without affecting ATP levels. Because of the key role of the 5′-AMP-activated protein kinase (AMPK) in energy homeostasis, we hypothesized that targeting glycolysis (MCT-blockade) in AMPK-null (Ampk−/−) cells should kill tumour cells from ‘ATP crisis’. We show that Ampk−/−-Ras-transformed mouse embryonic fibroblasts (MEFs) maintained ATP levels and viability when glycolysis was inhibited. In MCT-inhibited MEFs treated with OXPHOS inhibitors the ATP level and viability collapsed in both Ampk+/+ and Ampk−/− cells. We therefore propose that the intracellular acidification resulting from lactic acid sequestration mimicks AMPK by blocking mTORC1, a major component of an ATP consuming pathway, thereby preventing ‘ATP crisis’. Finally we showed that genetic disruption of Mct4 and/or Ampk dramatically reduced tumourigenicity in a xenograft mouse model suggesting a crucialrolefor these two actors in establishment of tumours in a nutrient-deprived environment. These findings demonstrated that blockade of lactate transport is an efficient anti-cancer strategy that highlights the potential in targeting Mct4 in a context of impaired AMPK activity. 相似文献
997.
998.
Nicolas Graillon Nathalie Degardin Jean Marc Foletti Magali Seiler Marine Alessandrini Audrey Gallucci 《Journal of cranio-maxillo-facial surgery》2018,46(10):1772-1776
Background
Secondary alveolar bone grafting in patients with clefts lip and palate is usually performed with iliac crest bone harvesting, however using bone substitute allow to avoid harvesting morbidity. The purpose of our study was to assess if the use of a bioactive glass ceramic is an acceptable alternative to iliac crest bone harvesting in alveolar clefts treatment.Methods
A prospective study including all patients who have benefited of alveolar grafting by GlassBONE? (Noraker, France), a synthetic resorbable bioactive glass 45S5 ceramic was conducted. The patients underwent clinical assessments and imaging check-up by dental panoramic radiography and CBCT.Results
Fifty-eight graftings were performed. The mean age at the time of the graft was 7.6 years. Hospitalization, social eviction and antalgic consumption were reduced. Bone continuity was achieved in 63.8% of the cases. Bilateral cleft and dental agenesia increased grafting failure. In the subgroup of 25 patients with isolated unilateral cleft without dental agenesis, 80% had bone continuity at one year. We noted 10.3% of alveolar fistula recurrence.Conclusion
The use of GlassBONE? in alveolar grafts simplifies the surgery procedure and the postoperative management, and ensures satisfactory mucosal healing, tooth eruption and bone continuity in two thirds of the followed grafts. 相似文献999.
Rabelo Gustavo Davi Coutinho-Camillo Claudia Kowalski Luiz Paulo Portero-Muzy Nathalie Roux Jean-Paul Chavassieux Pascale Alves Fabio Abreu 《Clinical oral investigations》2018,22(2):783-790
Clinical Oral Investigations - The aim of the study was to evaluate the mandible cortical bone changes in patients with oral squamous cell carcinoma (OSCC). Twenty patients who underwent some... 相似文献
1000.
Nathalie Jouve Richard Bachelier Nicolas Despoix Muriel G. Blin Maryam Khalili Matinzadeh Stphane Poitevin Michel Aurrand‐Lions Karim Fallague Nathalie Bardin Marcel Blot‐Chabaud Frdric Vely Franoise Dignat‐George Aurlie S. Leroyer 《International journal of cancer. Journal international du cancer》2015,137(1):50-60
CD146 is an adhesion molecule expressed by both melanoma and endothelial cells and thus is well positioned to control melanoma extravasation. Nevertheless, during melanoma metastasis, the involvement of CD146 expressed within tumor microenvironment has never been analyzed. To investigate whether host CD146 mediates the extravasation of melanoma cells across the endothelium, we generated CD146 KO mice. We demonstrated that host CD146 did not affect melanoma growth or tumor angiogenesis but promoted hematogenous melanoma metastasis to the lung. Accordingly, the survival of CD146‐deficient mice was markedly prolonged during melanoma metastasis. Interestingly, vascular endothelial growth factor‐induced vascular permeability was significantly decreased in CD146 KO mice. We also provided evidence that VEGF‐induced transendothelial migration of melanoma cells was significantly reduced across CD146 KO lung microvascular endothelial cells (LMEC). CD146 deficiency decreased the expression of VEGFR‐2/Ve‐cadherin and altered focal adhesion kinase (FAK) activation in response to VEGF. In addition, inhibition of FAK phosphorylation reduced transmigration of B16 melanoma cells across WT LMEC at the same level that across CD146 KO LMEC. Altogether, we propose a novel mechanism involving the VEGF/CD146/FAK/Ve‐cadherin network in melanoma extravasation across the vessel barrier that identifies CD146‐targeted therapy as a potential strategy for the treatment of melanoma metastasis. 相似文献