全文获取类型
收费全文 | 1389篇 |
免费 | 113篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 22篇 |
儿科学 | 94篇 |
妇产科学 | 20篇 |
基础医学 | 270篇 |
口腔科学 | 26篇 |
临床医学 | 110篇 |
内科学 | 266篇 |
皮肤病学 | 15篇 |
神经病学 | 151篇 |
特种医学 | 35篇 |
外科学 | 140篇 |
综合类 | 5篇 |
预防医学 | 162篇 |
眼科学 | 8篇 |
药学 | 51篇 |
肿瘤学 | 135篇 |
出版年
2024年 | 2篇 |
2023年 | 32篇 |
2022年 | 49篇 |
2021年 | 99篇 |
2020年 | 73篇 |
2019年 | 72篇 |
2018年 | 102篇 |
2017年 | 44篇 |
2016年 | 64篇 |
2015年 | 61篇 |
2014年 | 56篇 |
2013年 | 83篇 |
2012年 | 107篇 |
2011年 | 103篇 |
2010年 | 64篇 |
2009年 | 52篇 |
2008年 | 60篇 |
2007年 | 58篇 |
2006年 | 58篇 |
2005年 | 43篇 |
2004年 | 36篇 |
2003年 | 43篇 |
2002年 | 26篇 |
2001年 | 5篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1979年 | 2篇 |
1972年 | 8篇 |
1939年 | 2篇 |
1933年 | 2篇 |
1925年 | 2篇 |
1912年 | 1篇 |
1911年 | 1篇 |
1910年 | 2篇 |
1904年 | 1篇 |
排序方式: 共有1510条查询结果,搜索用时 203 毫秒
1.
Alcohol is an important risk factor for human oesophageal cancer. There is evidence from epidemiological studies that some
specific alcoholic drinks, e.g. Calvados apple brandy, are associated with a greater risk than others. Alcohol induces cytochrome
P450 2E1 (CYP2E1) and the hypothesis was tested that different alcoholic beverages, containing a variety of alcoholic compounds,
could differentially induce expression of cytochrome P450 enzymes. Twelve groups of five rats each were treated for 3 days
with different alcoholic beverages (ethanol alone, whisky, farm-produced or commercial Calvados brandy, beer, cider, wine)
adjusted to 4, 10 or 20% of ethanol in drinking water. Immunoblotting using a monoclonal antibody specific for rat CYP2E1
revealed a single protein band in liver microsomes. Densitometric quantitation of microsomal proteins demonstrated a significant
two-, three- and sixfold increase in band intensity after treatment with ethanol concentrations of 4, 10 and 20% respectively,
compared to control rats drinking water alone. There was a dose-dependent increase in liver microsomal metabolism of CYP2E1
substrates (para-nitrophenol and dimethylnitrosamine) in ethanol-treated rats. However, there were no significant differences
in the level of CYP2E1 protein or enzymatic activity between the different alcoholic beverages at the same ethanol concentration.
There was a slight increase in hepatic CYP1A-related enzymatic activities in the alcohol-treated rats compared to the controls,
but no difference between the treated groups either with dose of ethanol or type of beverage. These data show that induction
of CYP2E1 with acute alcohol treatment is predominantly determined by the ethanol content of the beverage.
Received: 10 February 1997 / Accepted: 26 May 1997 相似文献
2.
3.
4.
Guido Martignoni Maurizio Pea Matteo Brunelli Marco Chilosi Alberto Zamó Manuela Bertaso Paolo Cossu-Rocca John N Eble Gregor Mikuz Giacomo Puppa Cecile Badoual Vincenzo Ficarra Giovanni Novella Franco Bonetti 《Modern pathology》2004,17(12):1455-1463
CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P=0.003) and mitotic figures (P=0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas. 相似文献
5.
Histologic distinction between malignant mesothelioma,benign pleural lesion and carcinoma metastasis
W. S. Kwee R. W. Veldhuizen R. P. Golding H. Mullink J. Stam R. Donner Mathilde E. Boon 《Virchows Archiv : an international journal of pathology》1982,397(3):287-299
Summary Thirty men and 7 women with malignant mesothelioma seen at the Free University Hospital from 1st January 1960 until 1st July 1981 were reviewed.The histological, histochemical and morphometrical findings are reported. These findings are compared with 25 cases of pleural metastatic carcinoma and 25 cases of reactive pleural lesions.Fourty-nine percent of malignant mesotheliomas produced hyaluronic acid, however all cases of pleural metastatic carcinomas failed to produce this substance. All cases of malignant mesothelioma were D-PAS negative while 15 cases of pleural metastatic carcinoma showed reactivity to D-PAS. All cases of malignant mesothelioma and 9 cases of metastases were CEA negative.To distinguish malignant mesothelioma from metastases it is advisable to perform the D-PAS staining first. If it is negative mesothelioma can be confirmed by showing hyaluronic acid activity. A positive CEA staining rules out mesothelioma. In our study it was shown that with these methods 18 of 37 mesotheliomas could be identified with certainty, and 22 of the 25 carcinoma metastases.Morphometrically the malignant mesotheliomas could not be distinguished from the metastases, however the reactive pleural lesions had smaller nuclei than the malignant cells with mean values below 30 mu2. In the malignant cases these values had a range from 36 to 101 mu2.In distinguishing between reactive pleural lesions and malignant mesothelioma the production of hyaluronic acid points to the malignant character of the lesion.Thus histochemistry and immunostaining are important in the distinction of malignant mesothelioma from metastases, while the value of morphometry lies mainly in the separation of reactive lesions from malignant mesothelioma. 相似文献
6.
Flat urothelial lesions of the urinary bladder have been recently discussed by the International Society of Urological Pathology (ISUP) in 1998 and more recently redefined by an international consultation held in Ancona, Italy in 2001. This paper summarizes and illustrates the recent literature about non-papillary lesions of the urinary bladder. Flat urothelial lesions include: epithelial abnormalities (reactive urothelial atypia and flat hyperplasia), preneoplastic lesion (dysplasia) and neoplastic non invasive carcinoma (carcinoma in situ) and a new category of presumed neoplastic lesions and conditions; the latter points out to a notion of tumor biology, which may help to the understanding of urothelial carcinogenesis. 相似文献
7.
Agns Buzyn Marina Ostankovitch Anne Zerbib Mathilde Kemula Francine Connan Bruno Varet Jean-Grard Guillet Jeannine Choppin 《European journal of immunology》1997,27(8):2066-2072
Chronic myeloid leukemia (CML) is characterized cytogenetically by a t(9;22) translocation which generates a hybrid bcr-abl gene, encoding a p210bcr-abl fusion protein. The induction in vitro of leukemia-specific T cells reactive with p210bcr-abl is a strategy developed for an immunological therapeutic approach in CML. Peptides from the junction region of this chimeric protein have been considered as potential targets for a cytotoxic response against leukemic cells. However, only a few peptides encompassing the two p210bcr-abl breakpoints have been shown to bind to the most common HLA class I molecules, which limits the number of patients who could benefit from this approach. We assume that the presence of chimeric BCR-ABL protein in leukemic cells may affect processing and delivery of peptides, possibly giving rise to new epitopes at the cell surface. We selected 162 peptides from the whole sequence of this protein, including 14 peptides of the b2a2 and b3a2 junctions, which had an anchor motif for a common HLA class I molecule. We tested their ability to bind to eight HLA class I molecules (HLA-A1, -A2, -A3, -A11, -B7, -B8, -B27, -B44). We identified 48 peptides from outside the junction region, with intermediate or strong binding capacities to these HLA class I molecules contrasting with only six junction peptides with a moderate binding capacity to HLA-A3/A11, -B8, or -B44 molecules. Moreover, cytotoxic T lymphocyte lines specific for various peptides outside the junction were generated from peripheral blood mononuclear cells of HLA-A2 or -B7 healthy donors and from one CML patient. These results contribute to evaluation of immunity to the BCR-ABL chimeric protein. Further studies are required to investigate whether such epitopes are correctly processed and presented by leukemic cells. 相似文献
8.
Matrix Metalloproteinase and Cytokine Profiles in Monocytes over the Course of Stroke 总被引:14,自引:0,他引:14
Mathilde Kouwenhoven Christian Carlstrõm Volkan Õzenci Hans Link 《Journal of clinical immunology》2001,21(5):365-375
Stroke is a common cause of death and disability in our society. Stroke is associated with changes in immune responses within the central nervous system as well as systemically. The cells contributing to such changes as well as the factors contributing to formation of the inflammatory infiltrate observed in stroke remain to be clarified. In this study, blood monocytes and corresponding mononuclear cells (MNC) were separated and examined in parallel within 4 days and 1–3 months after onset of ischemic stroke. Numbers of TNF--, IL-12-, IL-6-, and IL-10-secreting cells and of cells expressing mRNA for matrix metalloproteinase (MMP)-1, -2, -7, -9 and tissue inhibitor of MMP (TIMP)-1 were studied. The TNF--, IL-12-, and IL-6-secreting monocytes and MNC were elevated during the acute phase compared to healthy controls. Such differences were not observed when stroke patients were examined during convalescence. The IL-10-secreting monocytes did not change over the course of stroke. Levels of monocytes expressing MMP-1, MMP-7 and TIMP-1 mRNA were elevated in the acute phase of stroke patients compared to convalescence and healthy controls, as were levels of MMP-1, -2, -7, -9 and TIMP-1 mRNA expressing blood MNC. The MMP-2 and -9 activity as measured by zymography also was higher in MNC supernatants in the acute phase of stroke compared to convalescence. The high levels of proinflammatory cytokines and MMPs in blood monocytes and MNC further demonstrate the presence of systemic aberrations in the acute phase of stroke. Such changes may contribute to the influx of blood-borne cells into the ischemic lesions during the acute phase of stroke. 相似文献
9.
We report on a boy with bilateral ectropion, ocular hypertelorism, bulbous nose, macrostomia with thin lips, abnormal ears, hypertrichosis of the forehead, neck and back, atrophic skin with hypoplastic nipples. Cause and inheritance are unknown. 相似文献
10.
Diagnostic utility of a p63/alpha-methyl-CoA-racemase (p504s) cocktail in atypical foci in the prostate. 总被引:1,自引:0,他引:1
Vincent Molinié Ga?lle Fromont Mathilde Sibony Annick Vieillefond Viorel Vassiliu Béatrix Cochand-Priollet Jean M Hervé Thierry Lebret Anne C Baglin 《Modern pathology》2004,17(10):1180-1190
Prostatic needle biopsy is the preferred method for diagnosing early prostate cancer, providing specific information. In cases of histological cancer mimics, a diagnosis of atypical small acinar proliferation suspected of but not diagnosed as malignancy can be made. In such cases, and in small focus carcinomas, pathologists use 34betaE12, cytokeratin (CK) 5/6 or p63 immunostaining to label basal cells, and alpha-methylacyl-CoA racemase (AMACR/p504s) immunostaining as a positive prostate cancer marker on two distinct slides. However, in cases of small foci, ambiguous lesions might disappear. The purpose of our study was to improve the sensitivity of a cocktail of two antibodies (p63/p504s) with a sample incubation on 260 prostatic specimens, in order to help make a decision in conjunction with standard histology and CK 5/6 immunostaining. We tested 101 small focus prostatic cancers, 104 atypical small acinar proliferation, 19 high-grade prostatic intraepithelial neoplasia, two atypical adenomatous hyperplasia and 34 benign mimics of cancer. After p63/p504s immunostaining, the final diagnoses retained were as follows: 154 prostatic cancers, 14 atypical small acinar proliferation, 30 high-grade prostatic intraepithelial neoplasia, three atypical adenomatous hyperplasia and 62 benign mimics of cancer. To differentiate malignant from benign lesions, we used the criteria of greater sensitivity to p504s/p63 (95%) than to CK 5/6 (57%) or p63 (86%), and higher specificity for p504s/p63 (95%) than for CK 5/6 (88%) or p63 (81%). With the p504s/p63 cocktail, 89% of the ambiguous lesions were classified vs 53% for CK 5/6. Combined use of the two antibodies, one (p504s) as a positive marker and the other (p63) as a negative marker, with a simple immunostaining procedure, may improve diagnostic performance, sensitivity and specificity, leading to a reduction in the risk of false negatives; this technique in cases of atypical small acinar proliferation should reduce the percentage of residual ambiguous lesions and the need for additional biopsies. 相似文献