全文获取类型
收费全文 | 376篇 |
免费 | 27篇 |
国内免费 | 8篇 |
专业分类
儿科学 | 33篇 |
妇产科学 | 14篇 |
基础医学 | 55篇 |
口腔科学 | 7篇 |
临床医学 | 40篇 |
内科学 | 96篇 |
皮肤病学 | 1篇 |
神经病学 | 6篇 |
特种医学 | 43篇 |
外科学 | 22篇 |
综合类 | 6篇 |
预防医学 | 40篇 |
眼科学 | 1篇 |
药学 | 17篇 |
肿瘤学 | 30篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 7篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 9篇 |
2014年 | 12篇 |
2013年 | 13篇 |
2012年 | 9篇 |
2011年 | 8篇 |
2010年 | 11篇 |
2009年 | 10篇 |
2008年 | 7篇 |
2007年 | 13篇 |
2006年 | 11篇 |
2005年 | 15篇 |
2004年 | 17篇 |
2003年 | 12篇 |
2002年 | 6篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 8篇 |
1998年 | 20篇 |
1997年 | 17篇 |
1996年 | 21篇 |
1995年 | 17篇 |
1994年 | 16篇 |
1993年 | 13篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 7篇 |
1989年 | 11篇 |
1988年 | 15篇 |
1987年 | 13篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 8篇 |
1976年 | 2篇 |
1972年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有411条查询结果,搜索用时 15 毫秒
1.
2.
Multiparameter flow cytometry as a tool for the detection of micrometastatic tumour cells in the sentinel lymph node procedure of patients with breast cancer 总被引:19,自引:0,他引:19 下载免费PDF全文
Leers MP Schoffelen RH Hoop JG Theunissen PH Oosterhuis JW vd Bijl H Rahmy A Tan W Nap M 《Journal of clinical pathology》2002,55(5):359-366
AIM: To investigate whether multiparameter flow cytometry (MP-FCM) can be used for the detection of micrometastasis in sentinel lymph nodes (SLNs) in breast cancer. METHODS: Formalin fixed, paraffin wax embedded sentinel lymph nodes (n = 238) from 98 patients were analysed. For each lymph node, sections for haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for cytokeratin (MNF116) were cut at three levels with a distance of 500 microm. The intervening material was used for MP-FCM. Cells were immunostained with MNF116, followed by an incubation with fluorescein isothiocyanate (FITC) labelled goat antimouse immunoglobulin. DNA was stained using propidium iodide. From each lymph node 100,000 cells were analysed on the flow cytometer. RESULTS: Thirty eight of the 98 patients with breast carcinoma showed evidence of metastatic disease in the SLN by one ore more of the three methods. In 37 of 38 cases where metastatic cells were seen in the routine H&E and/or IHC, more than 1% cytokeratin positive cells were detected by MP-FCM. In 24 patients, metastatic foci were more than 2 mm (macrometastasis) and in 14 these foci were smaller than 2 mm (micrometastasis). In three of these 14 cases, MP-FCM revealed positive SLNs, although this was not seen at first glance in the H&E or IHC sections. After revision of the slides, one of these three remained negative. However, MP-FCM analysis of the cytokeratin positive cells showed an aneuploid DNA peak, which was almost identical to that of the primary breast tumour. Duplicate measurements, done in 41 cases, showed a 99% reproducibility. In five of 14 patients with micrometastasis, one or two metastatic foci were found in the non-SLN. However, in 15 of 24 macrometastases multiple non-SLNs were found to have metastatic tumour. All micrometastases except for the remaining negative one mentioned above showed only diploid tumour cells, despite the fact that their primary tumours contained both diploid and aneuploid tumour cells. In primary tumours with more than 60% aneuploid cells, predominantly aneuploid macrometastasis were found, whereas diploid primary tumours only showed diploid micrometastases or macrometastases in their SLN. Aneuploid SLN macrometastases were associated with non-SLN metastases in five of seven patients, whereas diploid cases showed additional non-SLN metastases in only seven of 16 patients. CONCLUSION: In all cases, MP-FCM was sufficient to detect micrometastatic tumour cells in a large volume of lymph node tissue from SLNs. In some cases it was superior to H&E and IHC staining. Approximately 30% of SLN micrometastases are accompanied by additional non-SLN metastases. The size of the aneuploid fraction (> 60%) in the primary tumour may influence the risk of having both SLN and non-SLN metastases. 相似文献
3.
Hydrosalpinges adversely affect markers of endometrial receptivity 总被引:22,自引:10,他引:22
Meyer WR; Castelbaum AJ; Somkuti S; Sagoskin AW; Doyle M; Harris JE; Lessey BA 《Human reproduction (Oxford, England)》1997,12(7):1393-1398
While in-vitro fertilization (IVF) was initially developed in women with
tubal factor infertility, recent clinical studies have suggested that the
presence of hydrosalpinges lowers implantation and pregnancy rates. We
postulated that these hydrosalpinges cause impaired endometrial
receptivity. A total of 103 women with hydrosalpinges were prospectively
evaluated, and compared with 55 infertile and 44 fertile controls. All
women had endometrial biopsies during the window of implantation, analysed
by conventional histological criteria, and also stained for three integrin
markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha
vbeta3). Women with hydrosalpinges (cases) expressed significantly less of
the alpha vbeta3 integrin compared with controls. There was no difference
in expression of alpha1beta1 or alpha4beta1 among groups. A significantly
greater number of cases had out of phase histology and missing alpha vbeta3
(type I defects) and absent integrin expression despite normal histological
maturation (type II) defects, compared with controls. Of 20 women with
impaired endometrial receptivity who were also biopsied after hydrosalpinx
surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven
percent of type I and 57% of type II defects were corrected
postoperatively. Using markers of endometrial receptivity, this study
demonstrates that inflammatory hydrosalpinges have an adverse effect on
endometrial receptivity, which in some cases may be overcome by surgical
treatment of the hydrosalpinx.
相似文献
4.
bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors 总被引:16,自引:0,他引:16
Proliferative expansion and apoptotic cell death play prominent roles in T
cell development. The molecular control of cell cycle progression and
apoptosis appear to be inter-connected since the Bcl-2 protein can inhibit
apoptosis and slow cell cycle progression in cortical thymocytes and mature
T cells, particularly during the transition from the quiescent state into
the cell cycle. Here the impact of bcl-2 transgene expression on
CD3-CD4-CD8- T cell progenitors was assessed. Bcl-2 enhanced the survival
of these progenitors at all of the four major differentiation stages, CD25-
CD44+ (pro-T1), CD25 + CD44+ (pro- T2), CD25 + CD44- (pro-T3) and
CD25-CD44- (pro-T4). However, it reduced cell cycling and slowed turnover
only in the pro-T4 subset. From an analysis of bcl-2 transgenic mice
expressing a TCR transgene or bearing a mutation in the scid or rag-1 gene
we conclude that Bcl-2 inhibits proliferation only of T cell progenitors
that are activated via the pre- TCR, not those stimulated via c-Kit and the
IL-7 receptor.
相似文献
5.
Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism 总被引:3,自引:0,他引:3
Baron J; Winer KK; Yanovski JA; Cunningham AW; Laue L; Zimmerman D; Cutler GB Jr 《Human molecular genetics》1996,5(5):601-606
Parathyroid hormone secretion is negatively regulated by a 7- transmembrane
domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that
activating mutations in this receptor might cause autosomal dominant
hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified,
in two families with ADHP, heterozygous missense mutations in the
Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of
50 normal controls had either mutation. We also identified a de novo,
missense Ca(2+)-sensing receptor mutation in a child with severe sporadic
hypoparathyroidism. The amino acid substitution in one ADHP family affected
the N-terminal, extracellular domain of the receptor. The other mutations
involved the transmembrane region. Unlike patients with acquired
hypoparathyroidism, patients with these mutations had hypercalciuria even
at low serum calcium concentrations. Their greater hypercalciuria
presumably reflected activation of Ca(2+)-sensing receptors in kidney
cells, where the receptor negatively regulates calcium reabsorption. This
augmented hypercalciuria increases the risk of renal complications and thus
has implications for the choice of therapy.
相似文献
6.
Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule 下载免费PDF全文
Bianca LW Bendermacher Joep AW Teijink Edith M Willigendael Marie-Louise Bartelink Harry R Büller Ron JG Peters Jelis Boiten Machteld Langenberg Martin H Prins 《The British journal of general practice》2006,56(533):932-937
BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease. 相似文献
7.
H F van den Ingh J Bara C J Cornelisse M Nap 《American journal of clinical pathology》1987,87(2):174-179
A series of 55 flow cytometric characterized colorectal adenomas was analyzed with four different monoclonal antibodies (Mabs) for the occurrence of M1 antigens (associated with gastric fucomucins) and one Mab for carcinoembryonic antigen (CEA). The antigens were detected with an indirect immunoperoxidase technic on paraffin sections after pretreatment with pronase for M1 antigens and without pretreatment for CEA. The staining pattern revealed different correlations with the various parameters, i.e., size, histologic type, atypia, and ploidy of the adenomas. Especially the cytoplasmic staining of anti-M1, Mab (1-13 M1) correlated well with aneuploidy (R = 0.43; P less than or equal to 0.001) and with the DNA index (R = 0.34; P less than or equal to 0.01). Staining of the anti-CEA Mab only correlated with the size of the adenomas (R = 0.29; P less than or equal to 0.03). It is concluded that the immunoreactivity of Mab (1-13 M1), which significantly correlated with aneuploidy, may be associated with malignant transformation in the adenoma-carcinoma sequence. 相似文献
8.
Electrocardiographic reference values and configurations were established in apparently healthy African grey (Psittacus erithacus; n=45) and Amazon (Amazona spp.; n = 37) parrots, using standard limb leads. In 31 of the African grey parrots and 32 of the Amazon parrots electrocardiograms were made during isoflurane-anaesthesia. Significant differences between anaesthetized and unanaesthetized birds were found only for the median heart rate and QT-interval (P<0.05). Significant differences between the two genera were found for the duration of the P- and T-waves, the voltage of the T-wave and for the mean electrical axis. Sinus arrhythmias and ventricular premature beats were present in 5 to 10% of the tracings. 相似文献
9.
Hepatocellular carcinoma, adenoma, and focal nodular hyperplasia. Comparative histopathologic study with immunohistochemical parameters 总被引:1,自引:0,他引:1
I A Koelma M Nap S Huitema R A Krom H J Houthoff 《Archives of pathology & laboratory medicine》1986,110(11):1035-1040
For the evaluation of differential diagnostic parameters, hepatocellular carcinoma (HCC, n = 26), liver cell adenoma (n = 4), focal nodular hyperplasia (n = 8), and secondary liver tumors (n = 15) were studied with histologic and immunohistochemical methods. The study was performed on formalin-fixed, paraffin-embedded tissue sections, and, in some cases, also on frozen sections. The diagnostic contribution of the demonstration of alpha-fetoprotein, alpha-antitrypsin, hepatitis B surface antigen, carcinoembryonic antigen (CEA), and biliary glycoprotein I (BGPI), compared with routine hematoxylin-eosin and reticulin stains was evaluated. For the differentiation between HCC, adenoma, and focal nodular hyperplasia, immunohistochemistry contributed less than the strict application of histologic criteria. Immunohistochemistry of CEA and BGPI, however, appeared to be of help in differentiating between primary and secondary liver tumors as follows: CEA is consistently absent in liver cell tumors, while a bile canalicular staining pattern was seen in 80% of HCC due to the presence of BGPI reactivity. 相似文献
10.
Semiquantitative estimation of steroid hormone receptors by immunohistochemistry applied to paraffin sections is common practice in surgical pathology. Flow cytometric (FCM) analysis of estrogen receptor (ER) and progesterone receptor (PR) levels provides a faster and more objective quantitative assay. However, a major problem in such FCM analyses of solid tumor samples is the admixture of tumor cells with normal epithelial, stromal, and inflammatory cells. The aim of the underlying study was to investigate the applicability of a recently developed multiparameter flow cytometric methodology for the accurate estimation of the fraction of steroid hormone receptor-positive tumor cells and to explore whether this multiparameter approach allows the detection of specific, clinically relevant subsets of tumors, based on a combination of ploidy level, steroid hormone receptor status, and cell cycle characteristics. For this purpose, samples of 42 breast cancer patients, from which routine immunohistochemistry for ER and PR also was available, were analyzed. From each case, a cell suspension was prepared from the paraffin block by applying a heating and short pepsin digestion step to 50-microm-thick sections. These cell suspensions were double-immunostained for cytokeratin to identify the epithelial cells, and ER or PR, whereas DNA was quantitatively stained with propidium iodide using an optimized protocol. In the entire group of breast tumors, the percentages of ER- and PR-positive cells were registered in the epithelial subfraction, in combination with DNA ploidy and S phase fraction (SPF). A significant correlation was found between the fraction of hormone receptor-positive cells as found by the immunohistochemical and FCM procedures. For ER, a correlation coefficient of r = .87 was found, and for PR r = .62, both P < .0001. It became clear that all the diploid breast tumors had more than 30% tumor cells positive for ER with a SPF lower than 10%, whereas aneuploid tumors contained on average a smaller percentage of steroid hormone receptor-positive cells, and simultaneously an SPF greater than 10%. Our results show that this multiparameter FCM analysis allows an objective and reproducible quantification of the fraction of steroid hormone receptor-positive cells in the relevant epithelial cell compartment in relation to DNA ploidy status and proliferative capacity in a single-tube assay. 相似文献