全文获取类型
收费全文 | 662篇 |
免费 | 14篇 |
国内免费 | 26篇 |
出版年
2022年 | 3篇 |
2021年 | 3篇 |
2020年 | 19篇 |
2019年 | 50篇 |
2018年 | 22篇 |
2017年 | 23篇 |
2016年 | 37篇 |
2015年 | 8篇 |
2014年 | 48篇 |
2013年 | 50篇 |
2012年 | 22篇 |
2011年 | 61篇 |
2010年 | 25篇 |
2009年 | 48篇 |
2008年 | 38篇 |
2007年 | 42篇 |
2006年 | 23篇 |
2005年 | 14篇 |
2004年 | 18篇 |
2003年 | 13篇 |
2002年 | 8篇 |
2001年 | 4篇 |
2000年 | 12篇 |
1999年 | 11篇 |
1998年 | 13篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 10篇 |
1992年 | 11篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 12篇 |
1982年 | 3篇 |
排序方式: 共有702条查询结果,搜索用时 15 毫秒
171.
天然抗癌药物紫杉醇的研究进展 总被引:13,自引:1,他引:12
本文论述了紫杉醇的作用机理、自然资源、分离提纯和检测、生源途径、化学合成及结构改造、组织培养等的研究概况与进展。 相似文献
172.
Lin G. LeMay June Kan-Mitchell Peter Goedegebuure William Harel Malcolm S. Mitchell 《Cancer immunology, immunotherapy : CII》1993,37(3):187-194
Twenty-five CD4+ cytotoxic T lymphocyte (CTL) clones were obtained from the peripheral blood or tumor tissues of melanoma patients undergoing active specific immunotherapy. Melanoma-reactive T cells were cloned by limiting dilution using either autologous or allogeneic melanoma cells to stimulate their proliferation. Sixteen of the clones reacted against autologous melanoma cells but not against the autologous lymphoblastoid cell line, which we defined as melanoma-specific. Optimal demonstration of the lytic activity of CD4+ CTL required a 16-h incubation period and an effectortarget cell ratio of 401. In addition, a 24-h pre-incubation of the target melanoma cells with 100 U interferon (IFN) consistently augmented lysis by these CD4+ CTL, increasing it from a mean level of 20% to one of 52%. Lysis by 8 of the 11 melanoma-reactive CD4+ T cell clones was exclusively HLA-class-I-restricted, as judged by blocking with monoclonal antibodies (mAb). Five of these HLA class-I-restricted clones were reactive only with the autologous melanoma cells, while the other 3 clones were also reactive with allogeneic melanoma cells. In all cases, the T cells and melanoma targets shared at least one HLA class I allele, usually HLA-A2, HLA-C3 or HLA-B62. Interestingly, lysis by 2 of the 11 clones was inhibited by both anti-HLA-class-I or -HLA-class-II mAb, while lysis by 1 other clone was inhibited by neither. HLA class I molecules and several accessory molecules were maximally expressed by the melanoma target cells, both in terms of distribution and copy number before IFN treatment. Thus, IFN may have acted by increasing the expression of melanoma-associated epitopes as presented by HLA class I (or HLA class II) molecules. A proportion of human CD4+CTL appeared to recognize melanoma-associated epitopes presented by the HLA class I molecule, although their lytic potency may be less than that of their CD8+ counterparts.This work was supported by USPHS grant R01-CA 36233, and a grant from the Concern Foundation for Cancer Research. 相似文献
173.
174.
《Bioorganic & medicinal chemistry letters》2014,24(16):3748-3752
A novel series of (7-aryl-1,5-naphthyridin-2-yl)ureas was discovered as dual ERK2 and Aurora B kinases inhibitors. Several analogues were active at micromolar and submicromolar range against ERK2 and Aurora B, associated with very promising antiproliferative activity toward various cancer cell lines. Synthesis, structure activity relationship and docking study are reported. In vitro ADME properties and safety data are also discussed. 相似文献
175.
Iwona ?akomska Bo?enna Golankiewicz Marzena Pe?czyńska Adam Opolski Lech Kozerski 《Inorganica chimica acta》2005,358(6):1911-1917
A series of platinum(II) complexes with 6,8-dimethylimidazo[1,5-a]-1,3,5-triazin-4(3H)-one (6,8-DiMe-4-O-IMT) (I) and 6,8-dimethyl-2-thioxo-2,3-dihydroimidazo[1,5-a]-1,3,5-triazin-4(1H)-one (6,8-DiMe-4-O-2-S-IMT) (II) of formula trans-[PtCl2(dmso)(6,8-DiMe-4-O-IMT)] (1a) and trans-[PtCl2(dmso)(6,8-DiMe-4-O-2-S-IMT)] (2a) have been prepared and characterized with 1H, 13C, 15N, 195Pt NMR and IR. Significant 15N NMR upfield coordination shifts (81-96 ppm) of N(7) atom indicate this nitrogen atom as a coordination site. The multinuclear NMR and IR spectra indicate the square planar geometry with N(7) bonded heterocycles, S-bonded dimethylsulfoxide and two trans chloride anions. The platinum(II) complexes were tested for their antiproliferative activity in vitro against the cells of four human cell lines: SW707 rectal adenocarcinoma, A549 non-small cell lung carcinoma, T47D breast cancer and HCV29T bladder cancer. The activity of (1a, 2a) was lower than that of cisplatin. 相似文献
176.
Kanazawa J Ohta S Shitara K Fujita F Fujita M Hanai N Akinaga S Okabe M 《Cancer immunology, immunotherapy : CII》2000,49(4-5):253-258
KM871 is a chimeric antibody recognizing ganglioside GD3, which is one of the major gangliosides expressed on the cell surface
of human tumors of neuroectodermal origin. This study demonstrates the antitumor activity of KM871 against human melanoma
xenografts in nude mice, and analyzes the effector function operating in mice. In a well-established tumor model, KM871 showed
antitumor activity against H-15 and SK-MEL-28 human melanoma but not against H-187 and G361 human melanoma when administered
intravenously 5 days/week for 2 weeks. The G361 tumor became sensitive when KM871 was first administered on the day of tumor
inoculation. In this assay, it was observed that almost all the mice were tumor-free, but a few mice developed tumors. Therefore,
we examined the amount and expression pattern of GD3 antigen on G361 tumors escaping from KM871 treatment, but no change was
observed. Next we examined the optimal administration schedule for KM871 in mice, using H-15 melanoma. KM871 showed antitumor
activity when administered intravenously either 5 days/week for 2 weeks or three biweekly doses. However, the effect of the
former schedule was stronger than three biweekly doses. To compare the effector function in humans and mice, we studied the
complement-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity and antibody-dependent macrophage-mediated
cytotoxicity of KM871 using complement or effector cells prepared from humans and mice. It was found that the antibody-dependent
cell-mediated cytotoxicity exerted by polymorphonuclear cells and antibody-dependent macrophage-mediated cytotoxicity were
the only antitumor mechanism of KM871 in mice. However their action was very weak compared with that in humans, and complement-mediated
cytotoxicity, which was strong in humans, was not observed in mice. Therefore, the antitumor activity of KM871 against human
melanomas evaluated by the nude mouse model might be underestimated. These results indicate that KM871 shows good antitumor
activity against GD3-positive human melanoma and the antitumor activity expected in humans might be superior to that of the
nude mouse model.
Received: 10 July 1999 / Accepted: 21 January 2000 相似文献
177.
Tumor-derived multiple chaperone enrichment by free-solution isoelectric focusing yields potent antitumor vaccines 总被引:2,自引:0,他引:2
Graner M Raymond A Akporiaye E Katsanis E 《Cancer immunology, immunotherapy : CII》2000,49(9):476-484
We have utilized a free-solution/isoelectric focusing technique (FS-IEF) to obtain fractions rich in multiple chaperone proteins
from clarified A20 tumor lysates. Vaccines prepared from chaperone-rich fractions are capable of providing protective immunity
in mice subsequently challenged intravenously with the same A20 B cell leukemia cells. This protection is at least equal to
that provided by purified, tumor-derived heat-shock protein 70, which was the best chaperone immunogen in our hands against
this aggressive murine leukemia model. Dosage escalation studies, however, revealed that increasing vaccine dosages actually
abrogated the protective effects. The physical nature of the enriched chaperones indicates that they are associated in complexes,
which may have implications for their function. FS-IEF is relatively simple, rapid, and efficient, thus making combined multi-chaperone
therapy feasible.
Received: 11 May 2000 / Accepted: 13 June 2000 相似文献
178.
179.
《Bioorganic & medicinal chemistry》2016,24(2):261-269
Clinical studies have shown enhanced anticancer effects of combined inhibition of Src and MEK kinases. Development of multi-target drugs against Src and MEK is of potential therapeutic advantage against cancers. As a follow-up of our previous studies, and by using molecular docking method, we designed and synthesized a new series of 9-anilinoacridines containing phenyl-urea moieties as potential novel dual Src and MEK inhibitors. The anti-proliferative assays against K562 and HepG-2 tumor cells showed that most of the derivatives displayed good cytotoxicity in vitro. In particular, kinase inhibition assays showed that compound 8m inhibited Src (59.67%) and MEK (43.23%) at 10 μM, and displayed moderate inhibitory activity against ERK and AKT, the downstream effectors of both Src and MEK. Moreover, compound 8m was found to induce K562 cells apoptosis. Structure–activity relationships of these derivatives were analyzed. Our study suggested that acridine scaffold, particularly compound 8m, is of potential interest for developing novel multi-target Src and MEK kinase inhibitors. 相似文献
180.
《Bioorganic & medicinal chemistry letters》2014,24(5):1334-1338
Baicalein (5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one), a major flavonoid extracted from the root of Scutellaria baicalensis Georgi (Chinese name: Huangqin), showed potent anti-proliferative activity against a broad panel of human cancer cell lines both in vitro and in vivo. A novel series of baicalein derivatives were synthesized by introducing a group to C6-OH and a nitrogen-containing hydrophilic heterocyclic ring to C7-OH via a length of 3 or 4-carbon chain in this study. The in vitro antiproliferative activities of the 30 derivatives against HepG2, A549, BCG-823 cancer cell lines were evaluated. Among them, 10 compounds exhibit more potent cytotoxicity than baicalein against the three cancer cell lines. The most potent compound 9b possesses highest anti-proliferative potency against HepG2, A549, and BCG-823 with an IC50 value of 2.0 μM, 0.8 μM and 3.2 μM, respectively. Preliminary mechanism studies with compound 9b using Annexin V/PI double-staining assay and DAPI staining assay indicated that 9b inhibits tumor cell proliferation potentially through inducing apoptosis. 相似文献