全文获取类型
收费全文 | 27467篇 |
免费 | 2592篇 |
国内免费 | 1425篇 |
学科分类
医药卫生 | 31484篇 |
出版年
2024年 | 78篇 |
2023年 | 428篇 |
2022年 | 855篇 |
2021年 | 1061篇 |
2020年 | 861篇 |
2019年 | 661篇 |
2018年 | 602篇 |
2017年 | 686篇 |
2016年 | 705篇 |
2015年 | 994篇 |
2014年 | 1353篇 |
2013年 | 1410篇 |
2012年 | 1281篇 |
2011年 | 1649篇 |
2010年 | 1459篇 |
2009年 | 1533篇 |
2008年 | 1539篇 |
2007年 | 1580篇 |
2006年 | 1424篇 |
2005年 | 1408篇 |
2004年 | 1331篇 |
2003年 | 1288篇 |
2002年 | 1116篇 |
2001年 | 1035篇 |
2000年 | 937篇 |
1999年 | 738篇 |
1998年 | 643篇 |
1997年 | 558篇 |
1996年 | 458篇 |
1995年 | 384篇 |
1994年 | 241篇 |
1993年 | 185篇 |
1992年 | 114篇 |
1991年 | 97篇 |
1990年 | 57篇 |
1989年 | 59篇 |
1988年 | 65篇 |
1987年 | 42篇 |
1986年 | 48篇 |
1985年 | 61篇 |
1984年 | 70篇 |
1983年 | 34篇 |
1982年 | 57篇 |
1981年 | 44篇 |
1980年 | 50篇 |
1979年 | 33篇 |
1978年 | 32篇 |
1977年 | 34篇 |
1976年 | 24篇 |
1975年 | 18篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
21.
Transplacental passage of mifepristone and its influence on maternal and fetal steroid concentrations in the second trimester of pregnancy 总被引:2,自引:0,他引:2
N C Hill M Selinger J Ferguson I Z MacKenzie 《Human reproduction (Oxford, England)》1991,6(3):458-462
The maternal and fetal endocrine effects of the maternal administration of the anti-progestin mifepristone in mid-pregnancy have been investigated. Mifepristone and the metabolite RU 42,633 were detected in the fetal circulation and in the amniotic fluid 4, 24 and 48 h after oral ingestion. Maximum fetal plasma concentrations of mifepristone occurred 4 h after treatment indicating rapid placental transfer of the drug. No significant changes in progesterone, cortisol, oestradiol or aldosterone concentrations were detected in the maternal circulation after mifepristone treatment. No significant changes occurred in the fetal progesterone, oestradiol or cortisol concentrations, but a significant increase in fetal aldosterone occurred 4 and 24 h after treatment. The significance of these results is discussed in relation to the possible therapeutic uses of mifepristone for inducing labour. 相似文献
22.
Chihaya Maesawa Gen Tamura Yasushi Suzuki Kaoru Ishida Kazuyoshi Saito Ryoichi Satodate 《Cancer science》1992,83(12):1253-1256
For the rapid and sensitive detection of p53 gene mutations in esophageal endoscopic biopsy specimens, we combined cell sorting with the polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) analysis. Mutations in exons 5–8 of the p53 gene were investigated by FCR-SSCF analysis using 103 sorted nuclei obtained from each endoscopic biopsy specimen of 16 patients with esophageal cancer. DNAs extracted from their respective surgical specimens were investigated by a conventional method of PCR-SSCP analysis. Mutations in the biopsy specimens were detected in 6 of the 12 aneuploid tumors but in none of the 4 diploid tumors. After tumor cell enrichment by cell sorting, one mutation in exon 8 became apparent, which could not be detected from the surgical specimen by a conventional method of PCR-SSCP analysis. This method should improve the sensitivity of detecting p53 gene mutations, and provides additional information concerning the DNA ploidy pattern in the tumors. 相似文献
23.
VEGF和p53在胰腺癌中的表达及意义 总被引:1,自引:0,他引:1
目的 探讨胰腺癌组织中血管内皮生长因子 (VEGF)及p5 3蛋白的表达及其临床病理意义。方法 采用SP免疫组织化学方法 ,对 46例胰腺癌组织中VEGF及 p5 3蛋白的表达进行检测。结果 VEGF与 p5 3表达率分别为 65 .2 %和 5 8.7%。p5 3表达与VEGF表达呈明显正相关(P <0 .0 5 )。VEGF表达与胰腺癌淋巴结转移 (P <0 .0 5 )和远处转移 (P <0 .0 1)显著相关 ,而与肿瘤大小 ,病理学分级无关 ,p5 3表达与胰腺癌远处转移 (P <0 .0 5 )显著相关 ,而与肿瘤大小 ,病理学分级及淋巴结转移无关。结论 在胰腺癌中 ,VEGF表达与 p5 3蛋白的表达呈正相关 ,在胰腺癌的转移中起重要作用 相似文献
24.
老年2型糖尿病患者胰岛素抵抗相关指标的检测和意义 总被引:1,自引:1,他引:0
目的:探讨老年2型糖尿病胰岛素抵抗(IR)及其相关性,为老年2型糖尿病的合理防治提供临床依据。方法:选择120例老年2型糖尿病患者,按胰岛素敏感指数(HOMA)胰岛素抵抗(HOMA-IR)50百分位点将患者分为两组:胰岛素相对敏感组(HOMA-IR<3.56)和胰岛素相对抵抗组(HOMA-IR≥3.56),比较体重指数(BMI)、腰/臀比(WHR)、血压、血生化学检查等指标。用年龄>40岁,<60岁的2型糖尿病患者做对照组。结果:两组老年患者在年龄、性别、舒张压、空腹血糖、胆固醇、高密度脂蛋白、糖化血红蛋白、HOMA胰岛β细胞功能方面无差异;但BMI、WHR、收缩压、甘油三脂、空腹胰岛素、HOMA-IR差异具有显著性。多线性回归分析后,只有腰/臀比、收缩压、甘油三脂、HOMA-IR存在统计学差异。老年患者与对照组相比,IR发生率明显增加,且两者腰/臀比、收缩压、甘油三脂方面也差异显著。结论:IR与老年2型糖尿病密切相关,是临床防治糖尿病的重要靶点。 相似文献
25.
26.
Martina Plísková Jan Vondrácek Borivoj Vojtesek Alois Kozubík Miroslav Machala 《Toxicological sciences》2005,83(2):246-256
Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are carcinogens suggested to be involved in development of human cancer. Several recent studies have reported that PAHs can activate estrogen receptors (ER), either directly or indirectly by producing estrogenic metabolites. We hypothesized that the activation of ER by PAHs or their metabolites could induce cell proliferation in estrogen-sensitive cells. In the present study, we found that two PAHs, benz[a]anthracene (BaA) and BaP, can stimulate proliferation of human breast carcinoma MCF-7 cells at concentrations 100 nM and higher. This effect was ER-dependent, because it was blocked by the pure antiestrogen ICI 182,780. Although both PAHs partially inhibited S-phase entry and DNA synthesis induced by 17beta-estradiol, they stimulated S-phase entry when applied to MCF-7 cells synchronized by serum deprivation. This was in contrast with model antiestrogenic aryl hydrocarbon receptor ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, which fully suppressed S-phase entry. BaP, which is a strong mutagen, was found to induce p53 tumor suppressor expression, a partial S-phase arrest and at higher concentrations also cell death. Pifithrin-alpha, a synthetic inhibitor of p53 activity, abolished both S-phase arrest and apoptosis induced by genotoxic PAHs, and it potentiated the proliferative effect of BaP. Thus, both genotoxic and nongenotoxic events seem to interact in the effects of BaP on cell proliferation. Taken together, our data indicate that both BaA and BaP can stimulate cell proliferation through activation of ER. The proliferative effects of these carcinogenic compounds might contribute to tumor promotion in estrogen-sensitive tissues. 相似文献
27.
28.
Dr. Elina Ikonen Armi Salo Mirja Somer Hannu Somer Leena Pääkkönen Leena Peltonen 《American journal of medical genetics. Part A》1992,43(4):753-758
A 15-year-old boy with a terminal deletion of the short arm of chromosome 4 is described. The patient has a mild clinical phenotype that is incompatible with Wolf-Hirschhorn syndrome. Careful neurological examination including CT scan did not show any signs of Huntington disease. The chromosomal breakpoint was analyzed by means of polymorphic DNA probes localized close to the tentative Huntington (HD) locus. The breakage has occurred between D4S43 and D4S90 loci and thus deletes part of the chromosomal candidate regions for the HD locus. © 1992 Wiley-Liss, Inc. 相似文献
29.
Zafer Sinik Turgut Alkibay Oumür Ataoglu Hasan Biri Sinan Sözen Nuri de Niz Uustünol Karaoglan Ibrahim Bozkirli 《International journal of urology》1997,4(6):546-551
Background :
The aim of this study was to examine nuclear p53 overexpression in transitional cell carcinoma of the bladder, adenocarcinoma of the prostate, and renal cell carcinoma.
Methods :
Forty-four pathologic specimens from 39 bladder cancer patients, 41 prostatic adenocarcinoma, and 39 renal cell carcinoma specimens were analyzed immunohistochemically with D07 monoclonal antibody to detect the expression of the mutant p53 gene. Overexpression was said to occur when the number of positively-stained tumor nuclei were≥ 10% in each specimen. p53 overexpression was correlated with the clinical and histopathological features of these cancers.
Results :
Nuclear p53 overexpression occurred in 18.2% of transitional cell bladder cancer specimens, 12.2% of prostate cancer specimens, and 17.9% of renal cell cancer specimens. Statistical analyses showed that grade, vascular invasion, and necrosis in bladder cancer, a high Gleason score in prostate cancer, and the 1-year mortality rate in renal cancer were significantly related with p53 nuclear overexpression (P<0.05).
Conclusion :
Using the D07 monoclonal antibody, nuclear p53 overexpression is relatively uncommon in urologic malignancies, and moderately correlates with several histopathological and clinical features of urologic malignancies. 相似文献
The aim of this study was to examine nuclear p53 overexpression in transitional cell carcinoma of the bladder, adenocarcinoma of the prostate, and renal cell carcinoma.
Methods :
Forty-four pathologic specimens from 39 bladder cancer patients, 41 prostatic adenocarcinoma, and 39 renal cell carcinoma specimens were analyzed immunohistochemically with D07 monoclonal antibody to detect the expression of the mutant p53 gene. Overexpression was said to occur when the number of positively-stained tumor nuclei were≥ 10% in each specimen. p53 overexpression was correlated with the clinical and histopathological features of these cancers.
Results :
Nuclear p53 overexpression occurred in 18.2% of transitional cell bladder cancer specimens, 12.2% of prostate cancer specimens, and 17.9% of renal cell cancer specimens. Statistical analyses showed that grade, vascular invasion, and necrosis in bladder cancer, a high Gleason score in prostate cancer, and the 1-year mortality rate in renal cancer were significantly related with p53 nuclear overexpression (P<0.05).
Conclusion :
Using the D07 monoclonal antibody, nuclear p53 overexpression is relatively uncommon in urologic malignancies, and moderately correlates with several histopathological and clinical features of urologic malignancies. 相似文献
30.
Comparison of p53 expression in proximal and distal gastric cancer: Histopathologic correlation and prognostic significance 总被引:2,自引:0,他引:2
Huihuan Tang MD Shuichi Hokita MD PhD Xiangming Che MD Masamichi Baba MD PhD Kuniaki Aridome MD PhD Fumio Kijima MD Gen Tanabe MD PhD Sonshin Takao MD PhD Dr. Takashi Aikou MD PhD 《Annals of surgical oncology》1997,4(6):470-474
Background: The overexpression of p53 has been found to be correlated with prognosis of some carcinomas, including gastric cancer, but
no studies have reported on its relationship to the location of gastric cancer. In the present study, we compared the p53
expression of proximal and distal gastric cancer concerning histopathology and prognosis.
Methods: A total of 170 tumors in the patients with proximal (80 cases) and distal (90 cases) gastric cancer were studied by immunohistochemical
methods.
Results: p53 immunopositivity was detected in 28.8% of all tumors. The p53-positive expression in proximal gastric cancer was higher
than in distal gastric cancer (38.8% vs. 20.0%, p<0.05). A 5-year survival analysis showed that there is no significant difference
between tumors that are p53 positive and p53 negative. No correlation was found between p53 expression and histopathology
of gastric cancer.
Conclusion: p53 nuclear staining is not useful as a prognostic indicator or as a parameter in gastric cancer. 相似文献