全文获取类型
收费全文 | 9044篇 |
免费 | 661篇 |
国内免费 | 70篇 |
专业分类
耳鼻咽喉 | 107篇 |
儿科学 | 237篇 |
妇产科学 | 96篇 |
基础医学 | 2396篇 |
口腔科学 | 313篇 |
临床医学 | 380篇 |
内科学 | 938篇 |
皮肤病学 | 220篇 |
神经病学 | 377篇 |
特种医学 | 304篇 |
外国民族医学 | 3篇 |
外科学 | 1370篇 |
综合类 | 419篇 |
预防医学 | 95篇 |
眼科学 | 131篇 |
药学 | 445篇 |
中国医学 | 96篇 |
肿瘤学 | 1848篇 |
出版年
2024年 | 12篇 |
2023年 | 118篇 |
2022年 | 136篇 |
2021年 | 191篇 |
2020年 | 240篇 |
2019年 | 208篇 |
2018年 | 226篇 |
2017年 | 227篇 |
2016年 | 212篇 |
2015年 | 290篇 |
2014年 | 425篇 |
2013年 | 754篇 |
2012年 | 330篇 |
2011年 | 394篇 |
2010年 | 339篇 |
2009年 | 367篇 |
2008年 | 403篇 |
2007年 | 391篇 |
2006年 | 381篇 |
2005年 | 299篇 |
2004年 | 318篇 |
2003年 | 302篇 |
2002年 | 292篇 |
2001年 | 291篇 |
2000年 | 264篇 |
1999年 | 295篇 |
1998年 | 219篇 |
1997年 | 221篇 |
1996年 | 193篇 |
1995年 | 195篇 |
1994年 | 165篇 |
1993年 | 143篇 |
1992年 | 135篇 |
1991年 | 103篇 |
1990年 | 100篇 |
1989年 | 74篇 |
1988年 | 63篇 |
1987年 | 67篇 |
1986年 | 58篇 |
1985年 | 64篇 |
1984年 | 69篇 |
1983年 | 33篇 |
1982年 | 41篇 |
1981年 | 32篇 |
1980年 | 31篇 |
1979年 | 19篇 |
1978年 | 21篇 |
1977年 | 9篇 |
1976年 | 6篇 |
1972年 | 2篇 |
排序方式: 共有9775条查询结果,搜索用时 15 毫秒
71.
The property of aerobic glycolysis commonly possessed by malignant cells points to a weakness in oxidative metabolism which has been equated in some tumours with partial uncoupling of oxidative phosphorylation. The suggestions are made, first, that this endogenous defect may account for spontaneous cell death
, and, second, that its accentuation would inflict extensive tumour injury upon sensitive neoplasms. Certain drugs not in current use for the treatment of malignant disease are known to be able to interfere selectively with energy metabolism in sensitive tumours to such an extent that widespread necrotisation ensues. The drugs activate an endogenous destructive mechanism that appears to require oxygen. Liminal therapy, the maintenance of continuous destructive pressure on sensitive growths in such a manner that maximal anti-tumour activity in terms of interference with energy production is not achieved at any one time, and under conditions in which the oxygen supply is only partly depleted, is put forward as a possible means of achieving complete and selective tumour destruction
. 相似文献
72.
K. -F. Bürrig H. Kastendieck 《Virchows Archiv : an international journal of pathology》1984,403(4):413-424
Summary Five localized fibrous tumours of the pleura (benign mesothelioma) were studied ultrastructurally in order to elucidate their histogenesis. The histological subtypes of this benign fibrous lesion of the visceral pleura, i.e. the cellular, the collagenous, and the hyaline, were separately analysed.The tumours are composed of undifferentiated mesenchymal cells, intermediate and differentiated fibroblasts as well as collagenous interstitial tissue. The varying distribution of these cell elements account for the various histological subtypes. Morphological similarities between the mesenchymal tumour cells and the superficial mesothelial cells, which are always separated from the true tumour tissue by an intact basement membrane, were not observed.The different cellular elements can be regarded as parts of a continuous spectrum of cytodifferentiation, in which the mature fibroblasts are derived via intermediate forms from the undifferentiated cells. It is concluded that the localized fibrous tumours of the pleura arise from immature mesenchymal stem cells, which seems to be normally found in the submesothelial layer of the visceral pleura. 相似文献
73.
Inter-laboratory and inter-observer reproducibility of immunohistochemical assessment of the Ki-67 labelling index in a large multi-centre trial 总被引:23,自引:0,他引:23
Mengel M von Wasielewski R Wiese B Rüdiger T Müller-Hermelink HK Kreipe H 《The Journal of pathology》2002,196(3):292-299
The calcium-binding protein S100A4 induces the metastatic phenotype in rodent models of breast cancer and its expression correlates strongly with reduced survival in human breast cancer. The expression of S100A4 in normal bladders and 101 bladder tumours has been studied using immunocytochemistry. Moderate or strong expression of S100A4 was found in 28% of the tumours, whilst the remaining tumours and normal urothelium either failed to stain or showed weak staining. S100A4 staining was more frequently observed in invasive bladder tumours than in non-invasive tumours (p<0.05). In invasive tumours, S100A4 staining was usually strongest in invasive regions and single infiltrating cells. Statistically significant associations were found between S100A4 expression and metastasis (p=0.0003) and reduced survival (p<0.0001). It is concluded that S100A4 expression may play an important role in bladder cancer and may identify a subgroup of patients at increased risk of metastasis who should be considered for adjuvant systemic therapy. 相似文献
74.
Quantitative expansion of structural genomic alterations in the spectrum of neuroendocrine lung carcinomas 总被引:3,自引:0,他引:3
Gugger M Burckhardt E Kappeler A Hirsiger H Laissue JA Mazzucchelli L 《The Journal of pathology》2002,196(4):408-415
The pathogenesis and interrelationships of neuroendocrine lung carcinomas are not well understood. Tissue macro-arrays prepared from surgical resection specimens from 35 patients with typical carcinoid (TC), six with atypical carcinoid (AC), 13 with large cell neuroendocrine carcinoma (LCNEC), and 15 with small cell lung carcinoma (SCLC) were investigated by fluorescence in situ hybridization (FISH) and immunohistochemistry. Hybridizations with locus-specific DNA probes demonstrated a high incidence of deletion for the tumour suppressor genes p53 and retinoblastoma (Rb), and for the oncogene cyclin D1, comparable in all carcinoma types. Similarly, an increase of DNA copy number for the Her-2/neu and c-myc oncogenes was noted in all neoplasms. A more detailed quantitative analysis of the results, however, demonstrated increasing numbers of cells harbouring these genomic alterations, from low-grade TC to highly malignant SCLC, with the exception of cyclin D1 deletion. Mutations of the p53 and Rb genes, as assayed by immunohistochemical studies, were observed at high incidence in high-grade carcinomas, compared with a low incidence in the low-grade carcinomas. Conversely, in all carcinoma types, neither membrane-bound Her-2/neu nor nuclear cyclin D1 was detected. It is concluded that structural genomic alterations are frequent in neuroendocrine lung carcinomas and that their occurrence may be underestimated by immunohistochemical studies alone. The quantitative expansion of the Rb, p53, c-myc, and Her-2/neu alterations towards high-grade carcinomas suggests common pathogenetic mechanisms in the spectrum of these neoplasms. 相似文献
75.
Heymann MF Joubert M Nemeth J Franc B Visset J Hamy A le Borgne J le Neel JC Murat A Cordel S le Bodic MF 《Histopathology》2000,36(5):421-432
AIMS: To study the clinical outcome of 82 cases of pancreatic neuroendocrine tumours classified according to the recent histological and prognostic classification of Capella. METHODS AND RESULTS: Eighty-two surgical cases of pancreatic neuroendocrine tumours were examined histologically with immunohistochemical staining of paraffin sections using streptavidin-biotin complex and application of antibodies against chromogranin A and 10 hormonal peptides. Classification in four groups correlated with long follow-up and outcome of these cases. Histological examination showed 30 group I, four group II, 41 group III and seven group IV tumours. Twenty-one (70%) of group I tumours were insulinomas, whereas 25% of group III tumours were glucagonomas and 25% were unclassified. Most group IV tumours were unclassified, showing no immunohistochemical staining with any of the 10 hormonal peptides tested. Outcome was clearly correlated with tumour group. Among the 14 patients who died of the disease, four had group IV and 10 group III tumours. Thus, unclassified asymptomatic tumours without immunohistochemical staining had a poorer prognosis than asymptomatic tumours with staining. CONCLUSION: This study validates the Capella classification as easy to apply and useful in predicting clinical outcome. 相似文献
76.
Koshy M Vijayananthan A Vadiveloo V 《Biomedical imaging and intervention journal》2005,1(2):e10-Dec;1(2):e10
Ovarian germ cell tumours are very rare and affect mainly young girls and women. Due to this, the conservation of reproductive potential is of great concern. One of the most remarkable advances in oncology is in the treatment of malignant ovarian germ cell tumours. Two histological groups are distinguished: dygerminomas, equivalent to testicular seminomas, and non-dysgerminomatous tumours. We report a case of a 30-year-old nulliparous woman who presented with persistent per vaginal bleeding and was found to have a malignant mixed germ cell tumour comprising of both embryonal carcinoma and choriocarcinoma. 相似文献
77.
Expression of oncogene products, anti-oncogene products and oncofetal antigens in intraductal papillary-mucinous neoplasm of the pancreas 总被引:1,自引:0,他引:1
A few previous studies have demonstrated the expression or mutations of oncogenes and anti-oncogenes as well as that of oncofetal antigens in intraductal papillary-mucinous neoplasm of the pancreas. In this study, we have investigated the immunohistochemical expression of oncogene (ras and c-erbB-2) and anti-oncogene (p53 and retinoblastoma [Rb]) products and oncofetal antigens (CEA, CA19-9 and DUPAN-2) in nine such tumours of the pancreas. In normal pancreas (5 cases), the Rb gene product and CA19-9 were expressed in all cases, while ras and c-erbB-2 gene products, p53 protein, CEA and DUPAN-2 were not expressed. In intraductal papillary-mucinous tumours (n = 9), ras, c-erbB-2, p53 and Rb gene products were present in 4/9 (44%), 7/9 (78%), 0.9 (0%) and 6/9 (67%) cases, respectively. CEA, CA19-9 and DUPAN-2 were expressed in 8/9 (89%), 9/9 (100%) and 2/9 (22%) cases respectively. In invasive ductal adenocarcinoma of the pancrease (7 cases), ras, c-erbB-2, p53 and Rb gene products were expressed in 3/7 (43%), 6/7 (86%), 2/7 (29%) and 3/ & (43%) cases respectively. CEA, CA19-9 and DUPAN-2 were expressed in 7/7 (100%), 7/7 (100%) and 6/7 (86%) cases, respectively. The extent and intensity of the expression of these antigens was greater in invasive ductal adenocarcinomas. These data suggest that activation of ras and c-erbB-2 oncogenes and inactivation of Rb anti-oncogene may contribute to the development and progression of intraductal papillary-mucinous tumours of the pancreas and that there is neo-expression of CEA and DUPAN-2 during the development and progression of these tumours. 相似文献
78.
Monocyte cytokine secretion induced by chemically-defined derivatives of Klebsiella pneumoniae. 下载免费PDF全文
Z Hmama G Lina C Vincent J Wijdenes G Normier H Binz J P Revillard 《Clinical and experimental immunology》1992,89(1):104-109
The capacity of a K. pneumoniae membrane proteoglycan (Kp-MPG) and four of its chemically defined derivatives to activate human monocytes was studied by measuring immunoreactive IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in culture supernatants. Monocyte culture supernatants were also tested for their comitogenic activity on concanavalin A-stimulated thymocytes and for their cytotoxic activity on the mouse fibroblastic L929 cell line. The four Kp-MPG derivatives were: (i) an acylpoly(1-3)galactoside (APG); (ii) an APG preparation submitted to acid hydrolysis which removed all fatty acids but left intact the galactose chain of APG (GC-APG); (iii) a preparation obtained by mild alkaline hydrolysis, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and (iv) a polymer of the latter compound (APG pol). Kp-MPG induced the synthesis of IL-1 beta, IL-6 and TNF-alpha with dose-responses and kinetics similar to those of Salmonella minnesota lipopolysaccharide (Sm-Re-LPS). APG pol and EFA-APG induced the secretion of the three cytokines with lower potency than Kp-MPG or Sm-Re-LPS. APG did not trigger any detectable cytokine production and GC-APG induced only borderline and inconsistent responses. Our data demonstrate the critical role of ester-linked C14 and C16 fatty acids in the triggering of monocyte response to Kp-MPG derivatives. 相似文献
79.
H
hler Kruger Gerken Schneider Meyer Zum BÜschenfelde Rittner 《Clinical and experimental immunology》1998,111(3):579-582
Cytokines such as TNF-α and interferon gamma (IFN-γ) are important for the elimination of infected hepatocytes during acute hepatitis B virus (HBV) infection. Two G versus A transitions in the TNF-α promoter region at positions ?308 and ?238 possibly influence TNF-α expression. We investigated these TNF-α polymorphisms in 71 patients with chronic HBV infection, in 32 subjects that had spontaneously recovered from acute HBV infection, and in 99 healthy controls. The ?238 A promoter variant was present in 18 (25%) of 71 patients with chronic HBV infection compared with two (6%) of 32 subjects with acute infection (P < 0.04), and seven (7%) of 99 controls (P < 0.003). By contrast, the prevalence of the variant at position ?308 was similar in all investigated groups. The observed differences could not be explained by linkage disequilibrium to HLA-B or -DRB1* alleles. These findings suggest an association between the TNF-α promoter polymorphism at position ?238 and the development of chronic HBV infection. This promoter variant appears to be linked to defective viral clearance. 相似文献
80.
Fibroblast growth factor 2 induces differentiation and apoptosis of Askin tumour cells 总被引:7,自引:0,他引:7
Kim MS Kim CJ Jung HS Seo MR Juhnn YS Shin HY Ahn HS Thiele CJ Chi JG 《The Journal of pathology》2004,202(1):103-112
Peripheral primitive neuroectodermal tumour (PNET)/Ewing's sarcoma (ES) and neuroblastoma (NB) are related tumours of neural crest origin with primitive neural characteristics. Fibroblast growth factor 2 (FGF2) is a critical signalling molecule for primitive neural crest cells. The treatment of NB cells with FGF2 variably affects biological characteristics such as growth and differentiation, while in PNET/ES, FGF2 predominantly induces apoptosis. The JK-GMS Askin tumour cell line can be induced to differentiate upon treatment with nerve growth factor (NGF), indicating the integrity of the cellular machinery necessary for differentiation. The present study assesses whether FGF2 can induce differentiation in JK-GMS cells. JK-GMS cells expressed high-affinity FGF receptors (FGFRs), and treatment with FGF2 induced phosphorylation of FGFR1 together with activation of extracellular signal-regulated kinases (ERK1/ERK2) and c-Jun N-terminal kinase (JNK). Subsequent biological effects were growth inhibition, neuronal differentiation, and apoptosis, and these changes were associated with increased expression of neurofilaments, reduction of c-myc and bcl-2 expression, and activation of caspase 3. Treatment of the cells with a specific inhibitor of the MAPK/extracellular signal-regulated kinase (MEK)-1, PD98059, predominantly inhibited the effects of FGF2 on growth, differentiation, and apoptosis, while an inhibitor of JNK reduced apoptosis, indicating that the ERK1/2 and JNK pathways are critical components of FGF2-mediated effects in JK-GMS cells. Additional comparative analyses of FGF2-mediated effects in two ES cell lines (CADO-ES, RD-ES) and a PNET cell line (SK-N-MC) showed pronounced differentiation in SK-N-MC, but not in CADO-ES or RD-ES cells. This study demonstrates that FGF2 can induce neuronal differentiation of PNET including Askin tumour. These findings clearly indicate that the FGF2-mediated signalling pathway plays a critical role in controlling the major properties of PNET cells and may provide a potential therapeutic target for PNET. 相似文献