全文获取类型
收费全文 | 1886篇 |
免费 | 57篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 18篇 |
妇产科学 | 38篇 |
基础医学 | 204篇 |
口腔科学 | 24篇 |
临床医学 | 104篇 |
内科学 | 567篇 |
皮肤病学 | 7篇 |
神经病学 | 214篇 |
特种医学 | 64篇 |
外科学 | 264篇 |
综合类 | 7篇 |
预防医学 | 41篇 |
眼科学 | 16篇 |
药学 | 137篇 |
中国医学 | 5篇 |
肿瘤学 | 229篇 |
出版年
2022年 | 18篇 |
2021年 | 16篇 |
2018年 | 15篇 |
2017年 | 15篇 |
2016年 | 21篇 |
2015年 | 17篇 |
2014年 | 23篇 |
2013年 | 36篇 |
2012年 | 60篇 |
2011年 | 53篇 |
2010年 | 43篇 |
2009年 | 42篇 |
2008年 | 72篇 |
2007年 | 60篇 |
2006年 | 89篇 |
2005年 | 71篇 |
2004年 | 67篇 |
2003年 | 68篇 |
2002年 | 81篇 |
2001年 | 88篇 |
2000年 | 86篇 |
1999年 | 71篇 |
1998年 | 22篇 |
1997年 | 23篇 |
1996年 | 25篇 |
1995年 | 15篇 |
1994年 | 20篇 |
1993年 | 19篇 |
1992年 | 54篇 |
1991年 | 51篇 |
1990年 | 49篇 |
1989年 | 43篇 |
1988年 | 56篇 |
1987年 | 48篇 |
1986年 | 50篇 |
1985年 | 37篇 |
1984年 | 34篇 |
1983年 | 35篇 |
1982年 | 13篇 |
1981年 | 14篇 |
1979年 | 31篇 |
1978年 | 16篇 |
1977年 | 17篇 |
1976年 | 14篇 |
1974年 | 11篇 |
1972年 | 15篇 |
1969年 | 13篇 |
1968年 | 14篇 |
1967年 | 11篇 |
1966年 | 11篇 |
排序方式: 共有1946条查询结果,搜索用时 15 毫秒
91.
Clinical Application of Serum Pepsinogen I and II Levels for Mass Screening to Detect Gastric Cancer 总被引:6,自引:2,他引:6
Kazumasa Miki Masao Ichinose Koichi B. Ishikawa Naohisa Yahagi Masashi Matsushima Nobuyuki Kakei Shinko Tsukada Masahiro Kido Satoshi Ishihama Yasuhito Shimizu Takehisa Suzuki Kiyoshi Kurokawa 《Cancer science》1993,84(10):1086-1090
A considerable number of gastric cancers derive from stomach mucosa where chronic atrophic gastritis is severe and extensive. Based on the fact that the serum pepsinogen levels provide a precise measure of the extent of chronic atrophic gastritis, we have devised a mass screening method involving serum pepsinogen measurement to identify subjects at high risk of gastric cancer. In 1991, we screened 4,647 workers (male: 4,113, female: 534, mean age: 49.0 years) at a Japanese company using this method. Out of 875 subjects (18.8%) with a serum pepsinogen I level of less than 50 μg/liter and a pepsinogen I/II ratio of less than 3.0, 676 subjects (14.5%) were selected for further investigation by endoscopy. This led to the detection of four subjects (0.086%) with gastric cancer (three in an early stage) and four subjects with adenoma. The cancer detection rate of this new screening method was comparable, and in some respects superior, to that of the traditional barium X-ray screening. Since the incidence of test-positive subjects was as low as 10% amongst subjects aged less than 40, this screening method appears to be especially useful for screening of younger generations. The new method is less expensive than the traditional barium X-ray and subjects experience little discomfort. Further, many serum samples can be quickly measured simultaneously. The results of this study have indicated that serum pepsinogen screening provides a valuable method for detecting gastric cancers. 相似文献
92.
In vitro studies were initiated to study the antitumour effect of protein-doxorubicin (DXR) conjugate on the growth of the multidrug resistant rat ascites hepatoma cell line, AH66DR. The 50% inhibitory concentration (IC50) for DXR in AH66DR cell line was 16 mumol l-1 (AH66 parental cell line, AH66P, IC50 was 0.08 mumol l-1). Treatment of AH66P and AH66DR cells with various concentrations of DXR or conjugates at equivalent concentrations of DXR was performed. The two types of conjugates used were bovine serum albumin (BSA)-DXR conjugate and immunoglobulin G (IgG)-DXR conjugate. Both of these conjugates showed potent dose-dependent inhibition of cell growth against AH66DR cells as compared with the cells treated with DXR or other controls. The IC50 for BSA-DXR and IgG-DXR conjugates in AH66DR cell line was 0.05 (equivalent DXR) mumol l-1 and 0.07 (equivalent DXR) mumol l-1, respectively. These values were similar to that of the AH66P treated with DXR. Cellular uptake and accumulation of DXR or BSA-DXR conjugate was also quantitated in both cell lines. The cellular concentration of DXR in AH66DR cells was 2-fold lower than that of AH66P cells throughout the experiment. In contrast, by the treatment of AH66DR cells with BSA-DXR conjugate, the intracellular drug concentration increased as a function of time up to 24 h (639.1 +/- 41.8, equivalent DXR, ng 10(-5) cells) and reached the same drug level as AH66P cells treated with DXR (617.9 +/- 17.3 ng-5 cells). Ammonium chloride treatment inhibited the effects of the conjugates but did not inhibit the free drugs. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate remained in the cells at relatively high concentration for a long time. These results indicate that by chemically modifying DXR, such as by conjugation of the drug with proteins, it may be possible to overcome multidrug resistance. 相似文献
93.
94.
Mutation and expression of the metastasis suppressor gene KAI1 in esophageal squamous cell carcinoma 总被引:50,自引:0,他引:50
Miyazaki T Kato H Shitara Y Yoshikawa M Tajima K Masuda N Shouji H Tsukada K Nakajima T Kuwano H 《Cancer》2000,89(5):955-962
BACKGROUND: KAI1/CD82, a tumor metastasis suppressor gene, is correlated inversely with the progression and invasion of several tumors. It also has been reported that the KAI1 gene is related to the tumor suppressor gene p53. This study was performed to clarify the correlation between KAI1/CD82 expression and clinicopathologic characteristics and p53 expression in patients with esophageal squamous cell carcinoma (ESCC). The authors also investigated mutation of the KAI1 gene coding region to determine whether this may reduce KAI1 expression in ESCC. METHODS: Using immunohistochemistry with anti-KAI1 polyclonal antibody and monoclonal antibody against p53, KAI1/CD82 and p53 expression were detected in 55 patients with ESCC who had undergone surgery. The authors examined the KAI1 gene mutation in 22 patients with ESCC by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and DNA sequencing. RESULTS: KAI1/CD82 expression was positive in 36 of 55 patients (65.5%). There was a significant inverse correlation between KAI1/CD82 expression and regional lymph node metastasis (P = 0.0045), distant metastasis (P = 0.0092), the number of lymph node metastases (P = 0.0019), and pathologic stage (P = 0.0046). The survival rates of KAI1/CD82 negative patients were poorer than those of positive patients (P = 0. 024). The correlation between KAI1 positive and p53 positive tumors was not statistically significant. None of the 22 patients with ESCC showed mutation of the KAI1 gene by PCR-SSCP. In one patient, there was polymorphism in the SSCP assay and DNA sequencing. CONCLUSIONS: The authors demonstrated immunohistochemically that the expression of KAI1 protein appeared to be correlated with lymph node metastasis. Mutation does not seem to be a mechanism for dysregulation of the KAI1 protein in ESCC. 相似文献
95.
Ovarian carcinoma in situ with germline BRCA1 mutation and loss of heterozygosity at BRCA1 and TP53 总被引:2,自引:0,他引:2
Werness BA Parvatiyar P Ramus SJ Whittemore AS Garlinghouse-Jones K Oakley-Girvan I DiCioccio RA Wiest J Tsukada Y Ponder BA Piver MS 《Journal of the National Cancer Institute》2000,92(13):1088-1091
BACKGROUND: The two-hit hypothesis for the genesis of cancer predicts that cancer can develop when the wild-type allele of a tumor suppressor gene is lost in an individual with a germline mutation in that gene. Neither loss of heterozygosity (LOH) for BRCA1 nor mutations of the TP53 (also known as p53) gene have been documented prior to invasion in ovarian cancers arising in women with germline BRCA1 mutations. Such documentation is difficult because lesions are rarely identified in ovarian epithelium. We, therefore, looked for LOH at microsatellite polymorphisms linked to the BRCA1 and TP53 tumor suppressor loci in an incidental carcinoma in situ of the ovary removed prophylactically from a woman with a germline BRCA1 mutation. METHODS: By use of laser-capture microdissection, we obtained pure populations of atypical ovarian epithelial cells and normal stromal cells. DNA was extracted, amplified with primers flanking polymorphic microsatellites linked to BRCA1 (D17S855 and D17S579) and TP53 (TP53 and D17S786), and analyzed for LOH at these microsatellites. We also tested for p53 expression in the abnormal epithelium by immunohistochemistry. RESULTS: Both of the markers linked to TP53 showed LOH, as did an intragenic BRCA1-linked marker (D17S855). The other microsatellite marker for BRCA1 was uninformative. Immunohistochemical staining with an antibody to p53 showed strong immunoreactivity confined to the atypical epithelium. CONCLUSIONS: BRCA1, as well as TP53, can undergo LOH prior to stromal invasion in BRCA1-associated ovarian cancer. Strong immunoreactivity for p53 suggests the presence of mutated p53 in these cells as well. These findings suggest that loss of function of these two tumor suppressor genes occurs early in ovarian carcinogenesis in BRCA1 mutation carriers. 相似文献
96.
97.
H. Shibuya K. Tsukada M. Takagi J. -I. Horiuchi S. Suzuki R. -I. Kamiyama 《Acta oncologica (Stockholm, Sweden)》1984,23(6):425-428
Identical Hodgkin's disease (HD) in monozygotic twins is presented together with a review of five previously reported pairs. The 12 reported cases of concordant HD in monozygotic twins had three characteristic features: a younger age than HD patients in general, a short interval between the onset of the disease in the two twins, and a similar histologic pattern in both twins. These rare cases may suggest that genetic and environmental factors are responsible for the occurrence of HD. 相似文献
98.
Y Tsukada 《The Japanese journal of physiology》1988,38(2):115-132
We are now at the stage of neurophysiology where learning and memory can be subjects of studies at a strictly molecular level, on the basis of the well-established finding that these higher nervous activities are sustained by, and formed in, the physicochemical events of specified neural mechanisms in the brain. As for the neurophysiological process of memory, much evidence has shown that short-term memory and long-term memory probably result from different molecular events in the brain, i.e., the former from reversible chemical modification of the synapses concerned, and the latter from reorganization of the synapses following synthesis of protein and its axonal transport, which causes the enduring consolidation of memories. How does the experience of individual organisms trigger the protein synthesis in the brain required for long-term memory? What is the role of protein molecules thus formed? What is the mechanism for the regulation of gene expression in the reorganization of neuronal circuits? Many such difficult problems need to be solved. Recently, cholinergic and glutamatergic neuron networks have attracted much attention because there is a strong possibility that they play a critical role in memory. The clinical implication of these findings in human memory deficit, as exemplified in senile dementia, further emphasizes the importance of neurobiological elucidation of the molecular mechanism for learning and memory. 相似文献
99.
Kazuhiro Tsukada Hideo Kato Isao Kurosaki Katsuyuki Uchida Yoshio Shirai Yutaka Aoyagi Yoshihisa Tsukada Hidenobu Watanabe Katsuyoshi Hatakeyama 《Journal of Hepato-Biliary-Pancreatic Surgery》1996,3(3):313-316
The successful treatment of hepatoid adenocarcinoma of the gallbladder with elevated serum alpha-fetoprotein (1243 ng/ml)
and segmental adenomyomatosis in a 58-year-old woman is described. The woman had alpha-fetoprotein (AFP)-producing carcinoma
of the gallbladder with regional lymph node metastasis and was treated by extended radical resection and postoperative adjuvant
chemotherapy. She is alive, showing normal serum AFP concentration and no recurrence, 57 months after surgery. The tumor cells
were stained immunohistochemically for AFP by the peroxidase anti-peroxidase method. Serum AFP reactivity to concanavalin
A and lentil lectin was similar to the pattern shown in hepatocellular carcinoma. Only a few cases of AFP-producing gallbladder
carcinoma have been reported and there have been no reports of long-term survivors. The combination of aggressive radical
resection and chemotherapy seems to have been effective for achieving long-term survival without liver metastasis. 相似文献
100.