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1.
The association of MTHFR and CBS variants with the doubling time and responsiveness to several chemodrugs was analyzed in 26 human cancer xenografts. The tumors homozygous for the absence of insertion (NN) for the CBS 844ins68bp were more chemosensitive than those with insertion (NI) to TS-1 (P=0.0048), suggesting a potential effect of this variant on fluoropyrimidine efficacy. Furthermore, the doubling time of tumors with a variant C allele (AC or CC) in MTHFR-A1298C was significantly longer than that of tumors with a normal allele (AA) (P=0.0008). Twenty-nine cellular proliferation-related genes were associated with MTHFR-A1298C genotyping and with the doubling time. 相似文献
2.
为了选择有效抗癌药提供临床使用以提高化疗疗效 ,用MTT分析 ,对 32例头颈肿瘤术后切下的标本进行体外细胞培养 ,再用 5 -Fu ,VCR ,MTX ,BLM ,DDP ,ADM ,PYM和CTX进行药敏试验 .结果 :对 5 -Fu敏感 2 7例 ,占 84 4% ,VCR敏感 7例 ,占 2 1 9% ;MTX敏感 2 0例 ,占 6 2 5 % ;BLM敏感 2 6例 ,占 81 3% ;DDP敏感 2 6例 ,占 81 3% ;ADM敏感 13例 ,占 40 6 % ;PYM敏感 2 1例 ,占 6 5 6 % ;CTX敏感 1例 ,占 3 1% .32例患者化疗效果满意 ,未出现明显的副作用 ,均存活 3a以上 ,术后常规检查及复查未见复发或转移 .结果表明 :MTT法用于肿瘤细胞药敏试验是一种准确、快速、简便、经济 ,不需放射性同位素 ,结果重复性好的方法 ,值得推广应用 . 相似文献
3.
目的筛选非小细胞肺癌药敏试验的条件。方法取25例非小细胞肺癌患者的瘤细胞,用四甲基偶氮唑盐(MTT)法观察9种化疗药物,在不同浓度、不同时间对瘤细胞的敏感性。结果9种化疗药物对瘤细胞的敏感性,有随着药物浓度的增加、作用时间的延长而增高的趋势,但每个药物都有各自的特点。结论非小细胞肺癌细胞MTT法药敏试验的浓度应为临床用药量的计算值,药物作用时间应以48h为宜。 相似文献
4.
目的 探讨ATP生物荧光肿瘤药敏检测技术 (ATP TCA )在乳腺癌化疗中的临床意义及应用价值。方法 选用 10种常用乳腺癌化疗药物 ,应用ATP TCA对 40例乳腺癌改良根治术标本、淋巴结活检和胸腔积液标本进行药敏检测 ,评估肿瘤细胞对化疗药物的敏感性。结果 ATP TCA对乳腺癌标本的可评价率为 90 .0 % ,化疗药物对乳腺癌的杀伤作用具有较强的个体差异性 ,10种化疗药物的敏感性分别为 :氟尿嘧啶 ( 5 Fu) 3 3 .3 %、顺铂 (DDP) 3 7.5 %、环磷酰胺 (CTX ) 2 9.2 %、足叶已甙 (VP 16)16.7%、丝裂霉素 (MMC) 2 2 .0 %、表阿霉素 (EPI) 41.7%、诺维本 (NVB) 45 .8%、阿霉素 (ADM ) 41.7%、泰素 (PTX) 5 4.2 %、羟基喜树碱 (HCPT) 2 5 .0 %。初步研究表明ATP TCA体外检测结果与实际临床疗效具有良好的相关性。结论 ATP TCA是准确的、可靠的肿瘤药敏检测技术 ,其检测结果与临床实际疗效具有良好相关性 ,可用于指导乳腺癌术后化疗 相似文献
5.
Absence of p53 Overexpression and Favorable Response to Cisplatin-based Neoadjuvant Chemotherapy in Urothelial Carcinomas 总被引:3,自引:0,他引:3
Yoshiyuki Kakehi Enver Özdemir Tomonori Habuchi Hirohiko Yamabe Takayuki Hashimura Yoshitaka Katsura Osamu Yoshida 《Cancer science》1998,89(2):214-220
It has been controversial whether cancer cells harboring loss or inactivation of the tumor suppressor p53 are resistant or sensitive to DNA-damaging agents including cisplatin and doxorubicin. Overexpression of mdm2 oncoprotein, a negative regulator of p53, is assumed to be an alternative to p53 dysfunction. Archival urothelial carcinoma specimens obtained from 60 patients prior to cisplatin-based chemotherapy were immunohistochemically studied for overexpression of p53 and mdm2. Thirty-two patients (group I) were treated with chemotherapy in the neoadjuvant setting, while 28 patients (group II) underwent chemotherapy for distant metastases or inoperable locoregional tumors. In group I, the responsiveness was correlated with staining status of p53 ( P =0.0225) and the combination of p53 and mdm2 ( P =0.0497). Negative staining of p53 and negative for both p53 and mdm2 could have predicted favorable response to chemotherapy in 16 of 18 (88.9%) and in 12 of 13 (92.3%) tumors, respectively. On the other hand, p53-positive and p53 and/or mdm2-positive staining could have predicted poor response only in 7 of 14 (50.0%) and 8 of 19 (42.1%) tumors, respectively. Disease-specific survival of the p53-negative group was significantly superior to that of the p53-positive group ( P =0.0086). Difference in survival did not become more significant when overexpression of mdm2 was taken into consideration ( P =0.0456). In contrast, in group II, there was no correlation of responsiveness to chemotherapy or survival with p53- or p53/mdm2-staining status. The patients with urothelial carcinomas negative for overexpression of p53 will benefit from neoadjuvant chemotherapy. From clinical viewpoint, however, p53 status alone or the combination of p53 and mdm2 status is not enough to identify those patients who will not benefit from the treatment. 相似文献
6.
Association of Loss of Heterozygosity at the p53 Locus with Chemoresistance in Osteosarcomas 总被引:4,自引:0,他引:4
Akiteru Goto Hiroaki Kanda Yuichi Ishikawa Seiichi Matsumoto Noriyoshi Kawaguchi Rikuo Machinami Yo Kato Tomoyuki Kitagawa 《Cancer science》1998,89(5):539-547
Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite insensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 ( p 53) and 13q14 ( Rb ) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p 53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p 53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss ( P <0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p 53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas. 相似文献
7.
Lajos Pusztai Savitri Krishnamurti Jorge Perez Cardona Nour Sneige Francisco J. Esteva Marina Volchenok Patricia Breitenfelder Shu-Wan Kau Shin Takayama Stanislaw Krajewski John C. Reed Robert C. Bast Jr. Gabriel N. Hortobagyi 《Cancer investigation》2005,22(2):248-256
It has been suggested that expression of anti-apoptotic proteins such as Bcl-2 or BAG-1 may confer cellular resistance to chemotherapy. A corollary of this hypothesis is that expression of these proteins may predict clinical response to treatment and that Bcl-2- or BAG-1-positive cells may selectively be enriched in postchemotherapy tissue specimens. The goal of this exploratory pilot study was to assess these two predictions by using immunohistochemistry in 29 paired pre- and postchemotherapy breast tissue specimens obtained from patients who underwent preoperative doxorubicin-based chemotherapy. All breast cancers expressed BAG-1 protein, and, in individual tumors, 40-100% of neoplastic cells stained positive for this protein. Homogenous cytoplasmic staining was typically observed, though neoplastic cells also showed nuclear staining in many specimens. We found no correlation between prechemotherapy expression of BAG-1 and subsequent pathological response to cytotoxic therapy. Paired pre- and posttreatment specimens showed similar levels of BAG-1 expression when residual tumor could be assessed. Bcl-2 was expressed in 55% of cancers and was localized to the cytoplasm. Absence of Bcl-2 expression in prechemotherapy specimens was associated with more frequent complete pathological response (58% vs. 20%; p = 0.04). However, similar to BAG-1, no difference between pre- and posttherapy expression of Bcl-2 was observed in neoplastic cells in paired tissue specimens. These observations suggest that BAG-1 contributes an important cellular function to breast epithelial cells, which is reflected by its ubiquitous expression in these tissues. However, it does not appear to determine response to doxorubicin-based chemotherapy. In contrast, lack of Bcl-2 expression was associated with a higher probability of complete pathological response to doxorubicin-based chemotherapy. 相似文献
8.
目的研究赤芍总苷(total paeonyglucosides,TPG)联合化疗药物卡铂(CBP)对人黑色素瘤A375细胞生长的抑制作用及相关机制。方法用TPG和CBP作用于体外培养的黑色素瘤细胞,SRB法检测药物对黑色素瘤细胞生长的作用,逆转录-聚合酶链反应法(RT-PCR)检测各组细胞PCNA、cyclin D、P21 mRNA的表达情况;Western blot法检测各组细胞PCNA、cyclin D、P21蛋白表达水平。结果 CBP处理组OD值较对照组明显降低,TPG联合CBP导致OD值进一步下降(P<0.01);CBP处理组黑色素瘤细胞PCNA和cyclin D mRNA和蛋白水平均较对照组显著降低(P<0.01),而P21 mRNA和蛋白水平则明显升高(P<0.01);TPG联合CBP作用于黑色素瘤细胞,PCNA和cyclin D mRNA和蛋白水平较CBP单独作用组下降更为明显;P21 mRNA和蛋白水平较CBP单独作用组升高更加显著。结论 TPG和CBP联合用药效果优于CBP单独用药,可进一步提高药物对肿瘤细胞的生长抑制,与降低PCNA和cyclin D表达、升高P21表达有关。 相似文献
9.
目的 观察中期因子(MK)基因小干扰RNA(siRNA)对膀胱癌细胞化疗药物敏感性的影响.方法 设计合成3个MK siRNA,转染人膀胱癌RT4细胞株,定量RT-PCR方法筛选下调MK mRNA效果最好的siRNA;以该siRNA转染RT4细胞后分组:空白对照组(Con-A)、空载对照组(Con-B)、错配对照组及MK siRNA 3.125、6.25、12.50、25.00、50.00、100.00、200.00 nmol/L组,实时定量RT-PCR和蛋白质印迹方法检测各组细胞MK表达情况;噻唑盐法检测紫杉醇(PTX)对各组细胞生长的影响;通过检测caspase-3活性和TUNEL方法观察癌细胞凋亡情况.结果 3个siRNA均明显下调MK mRNA水平,以S3效果最好.PTX组、Con-A十PTX组、Con-B+PTX组、siRNA 12.50 nmol/L组、3.125 nmol/L+PTX组、siRNA 6.25 nmol/L+PTX组、siRNA 12.50nmol/L+PTX组肿瘤细胞抑制率分别为(18.21±0.36)%、(18.19±0.29)%、(17.89±0.33)%、(1.86±0.52)%、(32.56±0.53)%、(53.83±0.38)%、(78.95±0.55)%.TUNEL结果显示,ConA、Con-B、siRNA 3.125、6.25、12.50 nmol/L组凋亡指数分别为(1.81±0.36)%、(1.89±0.38)%、(5.56±0.58)%、(9.68±0.55)%和(15.25±0.56)%.结果 MK基因siRNA可增强膀胱癌细胞化疗敏感性,诱导凋亡是其重要机制之一. 相似文献
10.
Nicola Baldini Katia Scotlandi Massimo Serra Katsuyuki Kusuzaki Toshiharu Shikita Maria C. Manara Daniela Maurici Mario Campanacci 《Journal of cancer research and clinical oncology》1992,119(2):121-126
Summary The reliability of a simple method evaluating the pattern of subcellular binding of Adriamycin (Adriamycin binding assay, ABA) as an index of sensitivity was demonstrated in different primary cultures and in sensitive and resistant cell lines of human osteosarcoma. After exposure to Adriamycin (10 g/ml for 30 min at 37°C), living sensitive cells showed selective intranuclear uptake of the drug, whereas in resistant cells no distinct subcellular distribution was observed. The binding pattern of Adriamycin in sensitive and in highly resistant cells was inversely related to the expression of P-glycoprotein. However, low levels of resistance in vitro, not detectable by increased levels of expression of P-glycoprotein, were revealed by ABA. The use of ABA in combination with the estimate of P-glycoprotein expression is recommended in clinical practice as an accurate means for predicting the sensitivity of osteosarcoma to Adriamycin.This study was supported by a grant from the Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.). 相似文献