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61.
Yi SY Park YS Kim HS Jun HJ Kim KH Chang MH Park MJ Uhm JE Lee J Park SH Park JO Lee JK Lee KT Lim HY Kang WK 《Cancer chemotherapy and pharmacology》2009,63(6):1141-1145
Purpose The phase II study was conducted to evaluate the efficacy and safety of irinotecan as salvage single-agent chemotherapy in
patients with advanced pancreatic cancer.
Methods Patients with measurable metastatic pancreatic cancer, progressive after previous gemcitabine-based chemotherapy were treated
with irinotecan 150 mg/m2 every 2 weeks. Treatment was repeated until disease progression or unacceptable toxicity.
Results Between March 2004 to February 2007, 33 patients were registered and treated with irinotecan monotherapy. The patients’ median
age was 59 years (range 36–70) and two had an ECOG performance status of 2. A total of 167 chemotherapy cycles were delivered
(median, 4; range 2–12). In an intent-to-treat analysis, three (9%) confirmed partial response and 13 patients with stable
disease were observed for a disease control rate of 48%. The median progression-free and overall survivals were 2.0 months
(95% CI, 0.7–3.3) and 6.6 months (95% CI, 5.8–7.4), respectively. Toxic effects were mainly gastrointestinal (nausea in 64%
of patients, diarrhea in 36%), Toxicity profiles were generally predictable and manageable, and there was no treatment-related
death.
Conclusions Second-line chemotherapy with single-agent irinotecan is marginally effective and well tolerated regimen for gemcitabine-pretreated
patients with advanced pancreatic cancer. 相似文献
62.
Xu Y Kolesar JM Schaaf LJ Drengler R Duan W Otterson G Shapiro C Kuhn J Villalona-Calero MA 《Cancer chemotherapy and pharmacology》2009,63(6):1073-1082
Purpose Based on the preclinical evidence of topoisomerase I (Topo-1) upregulation by mitomycin C(MMC) and decreased NF-κB activation
by celecoxib, we evaluated combinations of irinotecan/MMC and irinotecan/MMC/celecoxib in patients with advanced solid malignancies.
Patients–methods Initially, patients received MMC on day 1 and irinotecan on days 2, 8, 15 and 22, every 6 weeks. MMC dose was fixed at 6 mg/m2 and cumulative doses of >36 mg/m2 were not permitted. Irinotecan was escalated in 25 mg/m2 increments. Due to late-onset diarrhea, the schedule was subsequently shortened to 4 weeks, omitting irinotecan on days 15
and 22. In the second part of the study, celecoxib 400 mg orally twice daily was added to irinotecan/MMC regimen. Potential
pharmacokinetic interactions and Topo-1 and DT-diaphorase (NQ01) gene expressions in peripheral-mononuclear cells were evaluated.
Results Forty-five patients were enrolled. Irinotecan 125 mg/m2 on days 2 and 8 in combination with MMC 6 mg/m2 on day 1 every 4 weeks is recommended for future studies; myelosuppression and diarrhea are dose-limiting. The addition of
celecoxib resulted in unacceptable toxicities despite reductions on irinotecan’s dose. No relevant pharmacokinetic interactions
occurred between irinotecan and MMC, and mean increases in Topo-1, were observed. Sixteen of 36 patients evaluable for response-assessment
had discernable anti-tumor activity, including 1 complete, 4 partial, 10 minor and 1 tumor marker response. Four patients
had prolonged (>4 months) disease-stability (stable disease, not included in CR or PR). Patients experiencing complete and
partial responses had higher increments in Topo-1 expression.
Conclusions Modulation of irinotecan by MMC is feasible, devoid of pharmacological interactions and active in solid malignancies. The
lack of improvement in therapeutic index does not support the addition of celecoxib. 相似文献
63.
Takane H Kawamoto K Sasaki T Moriki K Moriki K Kitano H Higuchi S Otsubo K Ieiri I 《Cancer chemotherapy and pharmacology》2009,63(6):1165-1169
Introduction To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes.
Case report A 66-year-old Japanese male diagnosed with left pharyngeal carcinoma (T2N2bM0, stage IVA) was treated with irinotecan (70 mg/m2) on days 1, 8 and 15 in combination with docetaxel (60 mg/m2) on day 1 of a 28-day cycle. After the first cycle, he suffered marked toxicities, including grade 4 diarrhea and febrile
grade 4 neutropenia. Plasma concentrations of irinotecan, SN-38 and SN-38G were measured, and extensive accumulation of SN-38
was observed. Genotyping of UGT1A1 and OATP1B1 proteins showed UGT1A1*6/*28 and SLCO1B1*15/*15, respectively, which are known to lead to extremely low glucuronidation and transport activities of substrate drugs.
Conclusion The severe toxicities in this patient are attributable to the extensive accumulation of SN-38, which may result from a synergistic
or additive effect of low metabolic (UGT1A1*6/*28) and transport (SLCO1B1*15/*15) capabilities. 相似文献
64.
Phase II study of irinotecan and carboplatin in patients with the refractory or relapsed small cell lung cancer 总被引:3,自引:0,他引:3
Hirose T Horichi N Ohmori T Ogura K Hosaka T Ando K Ishida H Noguchi H Adachi M 《Lung cancer (Amsterdam, Netherlands)》2003,40(3):333-338
We examined the safety and efficacy of the combination of irinotecan plus carboplatin in patients with refractory or relapsed small cell lung cancer (SCLC). Patients with previously treated SCLC were eligible. Patients were treated every 3 weeks with carboplatin (with a target area under the concentration versus time curve of 5 mg min/ml using the Calvert formula on day 1) plus irinotecan (50 mg/m2 on days 1 and 8). From May 2000 to January 2002, 24 patients were eligible. None of the 22 patients achieved a complete response, but 15 achieved a partial response with an overall response rate of 68.2% (95% confidence interval, 45.1–86.1%). In 13 patients with sensitive disease, the response rate was 92.3% (95% confidence interval, 64.0–99.8%). The median survival time (MST) was 194 days (range 27–605 days). The MST did not differ significantly between patients with sensitive disease (245 days) and those with refractory disease (194 days, P=0.88). One patient died of treatment-related sepsis. Grade 3–4 hematologic toxicities included leukopenia in 58% of patients, neutropenia in 63%, thrombocytopenia in 58%, and anemia in 67%. Grade 3 diarrhea developed in 21% of patients and grade 3–4 infection in 13%. No patients had grade 4 diarrhea or grade 3–4 nausea and vomiting. This regimen is effective and well tolerated in patients with relapsed or refractory SCLC. However, the search for even more active regimens should be continued. 相似文献
65.
Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan, and radiotherapy as neoadjuvant therapy for rectal cancer 总被引:3,自引:0,他引:3
Hofheinz RD Horisberger K Woernle C Wenz F Kraus-Tiefenbacher U Kähler G Dinter D Grobholz R Heeger S Post S Hochhaus A Willeke F 《International journal of radiation oncology, biology, physics》2006,66(5):1384-1390
PURPOSE: To establish the feasibility and efficacy of chemotherapy with capecitabine, weekly irinotecan, cetuximab, and pelvic radiotherapy for patients with locally advanced rectal cancer. METHODS AND MATERIALS: Twenty patients with rectal cancer (clinical Stage uT3-T4 or N+) received a standard dosing regimen of cetuximab (400 mg/m(2) on Day 1 and 250 mg/m(2) on Days 8, 15, 22, and 29) and escalating doses of irinotecan and capecitabine according to phase I methods: dose level I, irinotecan 40 mg/m(2) on Days 1, 8, 15, 22, and 29 and capecitabine 800 mg/m(2) on Days 1-38; dose level II, irinotecan 40 mg/m(2) and capecitabine 1000 mg/m(2); and dose level III, irinotecan 50 mg/m(2) and capecitabine 1000 mg/m(2). Radiotherapy was given to a dose of 50.4 Gy (45 Gy plus 5.4 Gy). Resection was scheduled 4-5 weeks after termination of chemoradiotherapy. RESULTS: On dose level I, no dose-limiting toxicities occurred; however, Grade 3 diarrhea affected 1 of 6 patients on dose level II. Of 5 patients treated at dose level III, 2 exhibited dose-limiting toxicity (diarrhea in 2 and nausea/vomiting in 1). Therefore, dose level II was determined as the recommended dose for future studies. A total of 10 patients were treated on dose level II and received a mean relative dose intensity of 100% of cetuximab, 94% of irinotecan, and 95% of capecitabine. All patients underwent surgery. Five patients had a pathologically complete remission and six had microfoci of residual tumor only. CONCLUSION: Preoperative chemoradiotherapy with cetuximab, capecitabine, and weekly irinotecan is feasible and well tolerated. The preliminary efficacy is very promising. Larger phase II trials are ongoing. 相似文献
66.
Masi G Cupini S Marcucci L Cerri E Loupakis F Allegrini G Brunetti IM Pfanner E Viti M Goletti O Filipponi F Falcone A 《Annals of surgical oncology》2006,13(1):58-65
Background The prognosis of unresectable metastatic colorectal cancer might be improved if a radical surgical resection of metastases
could be performed after a response to chemotherapy.
Methods We treated 74 patients with unresectable metastatic colorectal cancer (not selected for a neoadjuvant approach) with irinotecan,
oxaliplatin, and 5-fluorouracil/leucovorin (FOLFOXIRI and simplified FOLFOXIRI). Because of the high activity of these regimens
(response rate, 72%), a secondary curative operation could be performed in 19 patients (26%).
Results Four patients underwent an extended hepatectomy, nine patients underwent a right hepatectomy, three patients underwent a left
hepatectomy, and three patients had a segmental resection. In five patients, surgical removal of extrahepatic disease was
also performed. In seven patients, surgical resection was combined with intraoperative radiofrequency ablation. The median
overall survival of the 19 patients who underwent operation is 36.8 months, and the 4-year survival rate is 37%. The median
overall survival of the 34 patients who were responsive to chemotherapy, but who did not undergo operation, is 22.2 months
(P = .0114).
Conclusions The FOLFOXIRI regimens we studied have significant antitumor activity and allow a radical surgical resection of metastases
in patients with initially unresectable metastatic colorectal cancer not selected for a neoadjuvant approach and also those
with extrahepatic disease. The median survival of patients with resected disease is promising. 相似文献
67.
Irinotecan hydrochloride (CPT-11) and mitomycin C as the first line chemotherapy for ovarian clear cell adenocarcinoma 总被引:3,自引:0,他引:3
Nishino K Aoki Y Amikura T Obata H Sekine M Yahata T Fujita K Tanaka K 《Gynecologic oncology》2005,97(3):893-897
OBJECTIVE: The purpose of this study was to report the results of adjuvant CPT-11 and MMC combination chemotherapy (CPT-M) for ovarian clear cell adenocarcinoma (OCCA). METHODS: Between 1996 and 2002, 20 patients with OCCA underwent primary debulking surgery and received 6 treatments of CPT-11 (140 mg/m2) in combination with MMC (7 mg/m2), 2 weeks apart with a space of 3-4 weeks between the 3rd and 4th treatment in adjuvant setting. Overall survival was compared with our historical control treated between 1983 and 1995, in which 14 patients with OCCA were treated with an initial optimal standard surgery and postoperative adjuvant cyclophosphamide, doxorubicin, and cisplatin (CAP) combination chemotherapy. RESULTS: Median age was 51 years old (range, 29-74). Twelve patients were in stage Ic, 1 in stage IIa, 5 in stage IIc, 1 in stage IIIc, and 1 in stage IV. Optimal cytoreduction with standard surgery was obtained in all 20 patients. The major toxicity with this regimen was neutropenia, which was reversible. The incidences of grade 3 and 4 neutropenia were 25% and 15%, respectively. The non-hematological toxicities were generally mild and well tolerated. One patient with stage Ic refused chemotherapy after the first cycle of CPT-M, and died of her disease 8 months after initial surgery. Five-year survival rate was 95.0% for CPT-M group, and 63.5% for CAP group (P = 0.042). Survival was significantly better for patients treated with CPT-M. CONCLUSION: This preliminary study shows that the combination of CPT-M appears to be safe and useful in patients with OCCA. Prospective randomized trials should be conducted to assess this regimen appropriate for women with OCCA. 相似文献
68.
69.
Combination chemotherapy with cisplatin and irinotecan in patients with adenocarcinoma of the small intestine 总被引:1,自引:0,他引:1
Makiko Ono Kuniaki Shirao Atsuo Takashima Chigusa Morizane Natsuko Okita Daisuke Takahari Yoshinori Hirashima Takako Eguchi-Nakajima Ken Kato Tetsuya Hamaguchi Yasuhide Yamada Yasuhiro Shimada 《Gastric cancer》2008,11(4):201-205
Background Small-bowel adenocarcinoma (SBA) is a rare tumor that has a poor response to chemotherapy and a poor prognosis. Treatment
strategies for SBA have not been clearly established.
Methods All patients with SBA treated using a combination of cisplatin and irinotecan (IP) as first-line chemotherapy at the National
Cancer Center Hospital in Japan between January 1999 and February 2007 were studied retrospectively.
Results Eight patients received IP as first-line chemotherapy. The median follow-up was 9.5 months (range, 4.2–37.5 months). The median
number of cycles of IP was three (range, 1–5). The overall response rate (complete or partial response) was 12.5% (complete
response, n = 0; partial response, n = 1). The disease control rate (complete or partial response or stable disease) was 75%. The median time to treatment failure
was 4.5 months (95% confidence interval, 0.9–5.8 months), and overall survival was 17.3 months (range, 1.9–21.3 months). The
most common adverse events were neutropenia and anorexia.
Conclusion IP combination chemotherapy may be an acceptable option for patients with SBA. Further studies are warranted to determine
the optimal chemotherapeutic regimen for SBA. 相似文献
70.
目的:观察伊立替康(开普拓)联合顺铂治疗晚期非小细胞肺癌(Non-Small cell lung cancer,NSCLC)的疗效以及不良反应。方法:经病理学或细胞学确诊的初治晚期NSCLC患者30例,男性18例,女性12例,中位年龄45岁(波动于33-56岁之间),KPS评分〉70。接受顺铂60-80 mg.(m^2)^-1联合开普拓60 mg.(m^2)^-1第1d、8d、15d静脉滴注,每4周重复。至少2周期以上,可评价疗效及不良反应。结果:全组PR7例,SD21例,PD2例,总有效率为23%。中位生存时间10.5个月,1年生存为率57%(17/30)。主要不良反应为延迟性腹泻和粒细胞减少。结论:伊立替康联合顺铂治疗晚期NSCLC疗效确切,不良反应发生率低,耐受性较好。 相似文献