全文获取类型
收费全文 | 17118篇 |
免费 | 2364篇 |
国内免费 | 608篇 |
出版年
2024年 | 75篇 |
2023年 | 604篇 |
2022年 | 497篇 |
2021年 | 1400篇 |
2020年 | 1368篇 |
2019年 | 1961篇 |
2018年 | 1284篇 |
2017年 | 848篇 |
2016年 | 761篇 |
2015年 | 953篇 |
2014年 | 1492篇 |
2013年 | 1793篇 |
2012年 | 776篇 |
2011年 | 909篇 |
2010年 | 497篇 |
2009年 | 599篇 |
2008年 | 544篇 |
2007年 | 571篇 |
2006年 | 530篇 |
2005年 | 431篇 |
2004年 | 347篇 |
2003年 | 309篇 |
2002年 | 255篇 |
2001年 | 160篇 |
2000年 | 137篇 |
1999年 | 121篇 |
1998年 | 130篇 |
1997年 | 105篇 |
1996年 | 75篇 |
1995年 | 82篇 |
1994年 | 67篇 |
1993年 | 61篇 |
1992年 | 60篇 |
1991年 | 57篇 |
1990年 | 30篇 |
1989年 | 35篇 |
1988年 | 31篇 |
1987年 | 29篇 |
1986年 | 13篇 |
1985年 | 28篇 |
1984年 | 21篇 |
1983年 | 6篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1974年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
Elizabeth A. Kingsley Teresa E. Carter Kevin D. Barrow Pamela J. Russell 《Cancer immunology, immunotherapy : CII》1996,41(6):348-354
A monoclonal antibody, BLCA-8, was raised against the human bladder cancer cell line, UCRU-BL-17CL. By flow cytometry and immunoperoxidase staining, this antibody was found to possess high specificity for bladder tumours, some reactivity with fetal tissues, and no reactivity with normal bladder, or any normal or malignant tissue. This high specificity and the stability of the antigen to the urinary environment suggest that BLCA-8 may have potential for use as an anti-bladder-cancer therapeutic agent. By thin-layer chromatography and autoradiography, BLCA-8 was found to bind four components within the neutral lipid fraction of a bladder cancer cell line, UCRU-BL-17/23. These components hadR
F values of 0.22, 0.16/0.15 (doublet), 0.12 and 0.08, and migrated below globoside, indicating the presence of more than four sugars. By enzyme-linked immunosorbant assay and thin-layer chromatography it was found that the binding of BLCA-8 to the lipid extract was increased by both mild alkaline hydrolysis and enzymatic treatments, indicating that adjacent phospholipids and glycolipids interfere with the accessibility of the antibody-binding site. Full biochemical characterisation of the BLCA-8 antigen is currently underway. 相似文献
82.
大肠癌中p53基因突变的研究 总被引:2,自引:0,他引:2
应用聚合酶链反应(PCR)──单链构型多态性(SSCP)结合银染法对14例大肠癌p53基因的第4、第5─6和第7外显子进行了点突变的研究,结果共检测出6例点突变,而且发现各外显子的突变频率存在差异。另外,利用购自ATCC的两个探针 (p53cDNA探针和pYNZ22探针)对大肠癌中p53基因的杂合性失去进行了研究,在14例大肠癌中共检出6例杂合性丢失。将点突变检测结果同杂合性丢失结果进行比较分析, 并着重探讨了大肠癌中p53基因失活导致肿瘤的作用方式。
Abstract:The exons 4-7 of p53 gene were examined in 14 colorectal Cancer patients by using PCR-SSCP-silver staining method.The results showed 6 cases of point mutation and the mutation frequencies of exons were different from each other.p53 cDNA and pYNZ22 VNTR were used as probes to examine LOH(Loss of heterozygosity)of 14 colorectal cancers.6 cases with LOH were found.The results of present research suggest that mutation and LOH of p53 gene are critical events in the progress and development of Cancer.There were different kinds of inactivation model of p53 gene in the process of development of cancer and transformation of cells. 相似文献
83.
Patricia L. Stranahan Jennifer Laroe Ronda McCombs Alex Goldsmith Iffat Rahim Mark Overland David E. Pettijohn 《Glycoconjugate journal》1996,13(5):741-747
Intratumoral phenotypic diversity is well documented with regard to tumor associated carbohydrate antigens (TACA). The factors which control the expression of these cell-surface oligosaccharides on different cells of the same tumor are not understood. We investigated the expression of a panel of mucin associated oligosaccharides in cell lines growing at different surface densities (number of cells per cm2 of growth flask). Results show that the apparent expression of extended Lea-Lex, Lea and Lex, sialyl Lea, Tn and sialyl Tn varies with density of growth by an invasive human squamous cell lung carcinoma cell line (NU6-1), a benign variant (NE-18) and the human lung epithelial cell line BEAS-2B. The results indicate that one of the factors influencing the apparent expression of mucin-associated oligosaccharides is cell-cell interactions.Abbreviations Mab
monoclonal antibody
- FIT
fluorescein isothiocyanate
- TACA
tumor associated carbohydrate antigen 相似文献
84.
T. Kupila-Rantala J. T. Dabek M. Hyvönen-Dabek 《Biological trace element research》1996,55(1-2):173-179
A new technique for investigation of elemental concentrations in subfractions of blood plasma is presented. The method is
composed of the ultrafiltration of plasma in the presence of ethylenediaminetetraacetic acid (EDTA) and the measurement of
the elemental composition by proton-induced X-ray emission (PIXE). The blood samples were collected from both healthy persons
and patients suffering from breast cancer. The main emphasis in this study was on the determination of loosely bound copper
(Cu) in plasma subfractions containing substances with molecular mass under 10,000, but zinc (Zn) and iron (Fe) contents of
these fractions were also determined. The detection limits obtained with this method for Cu, Zn and Fe were ≈10 ppb (wet wt). 相似文献
85.
Lino Piccinini Paola Borella Annalisa Bargellini Cristina Incerti Medici Alessandra Zoboli 《Biological trace element research》1996,51(1):23-30
The purpose of our study was to investigate the relationship between plasma and hair levels of Se, Zn, and Cu, and cancer.
We selected a total of 66 patients affected by either breast (38) or lung (28) cancer. They entered into the study at the
onset of disease, and before any chemical or radiotherapy. Controls were randomly selected among healthy people and were matched
for sex, age, smoking habits, and residence. In the group of breast cancer, a significant decrease in hair Se was found compared
to controls (p<0.01), whereas plasma Se was only slightly decreased. No difference between cases and controls was detected in both hair
and plasma levels of Zn and Cu. Subjects who developed lung cancer were significantly lower in hair Zn (p<0.05) and Cu (p<0.01) than controls, whereas there was no difference with regard to Se. In addition, plasma Cu of these patients was increased
as compared to controls. 相似文献
86.
Focusing our effort on the importance of FUra scheduling we have tested the hypothesis that pulse and continuous infusion (CI) of the fluoropyrimidine have different mechanisms of cytotoxicity. Our initial approach was to compare the mechanism of resistance of a cell line resistant to a short term exposure to FUra (HCT-8/FU4hR) to that of a cell line resistant to a prolonged exposure to the fluoropyrimidine (HCT-8/FU7dR). Cytotoxicity studies showed that HCT-8/FU4hR cells were still sensitive to FUra given as a 7-d exposure, suggesting different mechanisms of resistance. Indeed, rapid recovery of TS activity after drug removal was evident in the HTC-8/FU7dR cell line while HCT-8/FU4hR cells were similar to the parental cell line with regard to both the degree of in situ TS inhibition by FUra and duration of inhibition after FUra removal. In contrast, labelling studies with [3H-6] FUra (4 h exposure, 100 M) showed that the incorporation of the fluoropyrimidine into RNA is significantly decreased in HCT-8/FU4hR cells as compared to parental HCT-8 cells.Given the lack of cross resistance between the two schedulesin vitro, a pilot trial was done on patients with colorectal cancer refractory to bolus FUra. On 15 patients failing after FUra+LV or FUra alone 1 PR, 3 MR, 3 SD and 8 P were observed, confirmng a certain degree of activity of CI FUra in patients clinically resistant to bolus FUra.Based on this rationale, a phase II trial of schedule-oriented biochemical modulation of FUra in advanced colorectal cancer patients was conducted, employing a hybrid regimen of 2 biweekly cycles of FUra bolus (600 mg/sqm), preceeded by (24 h interval) methotrexate, 200 mg/sqm (in order to maximize the RNA effect of the drug) alternating with FUra continuous infusion, 200 mg/sqm daily for 3 weeks, modulated by leucovorin, 20 mg/sqm weekly bolus (in order to maximize the DNA effect).Thirty-three consecutive patients (median ECOG PS 1) with advanced measurable colorectal cancer and no prior therapy for metastatic disease entered the study, from February 1992 to August 1993. Three complete and 13 partial responses were obtained among these 33 patients (RR=48%, 95% confidence limis, 31–66%). After a median follow-up time of 23 months, 16 patients are still alive. The median progression free survival and overall survival were 9.6 and 20.8 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle was: mucositis 6%, diarrhea 3% and vomiting 3% for the bolus part and 21%, 3% and 6% respectively, for the continuous infusion part of the regimen. Hand-foot syndrome occurred in 27% of the patients treated with the continuous infusion regimen.In conclusion, this experimental and clinical project has generated a novel regimen of schedule oriented biochemical modulation that is twice as active and half as toxic compared to bolus FU+LV given with either the daily x 5 or the weekly schedule. This high clinical activity is very encouraging, especially considering that 1) consecutive patients were entered, 2) the responses were independently reviewed, 3) the progression free survival and survival were much longer than those actually reported for this disease, 4) the toxicity of the program, in particular the bolus regimen, was relatively low allowing further intensification. 相似文献
87.
The immunomodulating effects of preoperative sizofiran (SPG) administration on regional lymph nodes were studied in patients
with stage III or IV head and neck cancer, by comparing the immunofunction of peripheral blood. The regional lymph nodes were
dissected surgically, and freshly obtained mononuclear cells were studied to investigate the interleukin-2 (IL-2) production,
the LAK and NK activities, and the quantitative analysis of the surface phenotype of the mononuclear cells. The results indicated
that SPG enhanced immunological activities in the regional lymph nodes, as shown by increased IL-2 production and cytotoxic
activities of the effector cells (NK, LAK), and increased helper T lymphocytes (CD4+) in the tumor-uninvolved lymph nodes. The immunofunction following SPG administration was attenuated, but was still augmented
in the regional lymph nodes with metastases. Therefore, SPG was found to be a biologic response modifier to enhance the immunofunctions
of the regional lymph node in patients with head and neck cancer. 相似文献
88.
朱明华 《中国组织化学与细胞化学杂志》1995,(1)
应用免疫组化方法,对32例乳腺癌组织中肿瘤抑制基因p53蛋白的表达和雌激素受体的状态分别进行了检测。结果32例中p53蛋白阳性18例,阳性率56.3%,18例伴有同侧腋下淋巴结转移者阳性13例(72.2%)3而14例无转移者阳性5例(35.7%)二组阳性率差异显著(PMO.05)。32例中雌激素受体阳性17例,18例伴转移者阳性8例(44.4%);14例无转移者阳性9例(64.3%)。结果表明,p53蛋白的异常表达与乳腺癌的浸润转移有关,结合雌激素受体的检查,可作为临床预后判断一个有价值的标志。 相似文献
89.
以人胃癌细胞BGC-823为模型,研究了毛喉萜(forskolin)对胃癌细胞中蛋白激酶C活性及其亚类基因表达的作用,同时也观察了毛喉萜对癌基因c-jun及抑癌基因p53表达的影响.结果表明,2×10~(-5)mol/L毛喉萜处理BGC-823细胞72h,细胞质、膜和细胞核PKC活性下降,PKC亚类β,γ基因表达被抑制,癌基因c-jun的表达也明显降低,而抑癌基因p53表达升高,上述变化可能是毛喉萜抑制胃癌细胞增殖等生理效应的重要分子事件。 相似文献
90.
Study of trace elements in blood of cancer patients by proton-induced X-ray emission (PIXE) analysis
Durosinmi M. A. Ojo J. O. Oluwole A. F. Akanle O. A. Spyrou N. M. 《Biological trace element research》1994,(1):351-355
Proton-induced X-ray emission (PIXE) analysis was employed to determine the concentrations of six elements in the plasma and
erythrocytes of 18 cancer subjects (15 males and 3 females) with neoplastic disorders and in 70 controls (35 males and 35
females). It was found that the concentrations of Br, K, and Zn were significantly elevated in the erythrocytes of the cancer
subjects compared to the controls, whereas the concentration of Fe was significantly depressed, but with no difference observed
in the concentration of Ca. In the plasma, the concentrations of Br, Cu, Ca, and K were significantly elevated, whereas the
concentrations of Fe and Zn were found to be significantly depressed compared to the controls. 相似文献