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51.
52.
Heponiemi T Elovainio M Kivimäki M Pulkki L Puttonen S Keltikangas-Järvinen L 《Social science & medicine (1982)》2006,63(5):1374-1382
This 14-year longitudinal study examined the independent association between perceived social support and the 5-year progression of depressive tendencies while taking into account the potential effects of childhood/adolescent anger and later hostility. From the on-going population based study of "Cardiovascular Risk in Young Finns", 553 male and 860 female participants responded to a revised version of Beck's Depression Inventory in 1992 and 1997. Hostility and perceived social support were assessed by self-rated questionnaires in 1992. Childhood/adolescent anger was assessed by parent-reports in 1983. Our results showed that higher levels of perceived social support were associated with the decrease of depressive tendencies after 5 years and lower levels of depressive tendencies prospectively and after 5 years. This association persisted after adjusting for childhood/adolescent anger and later hostility. In addition, hostility was strongly related to the 5-year increase of depressive tendencies and higher levels of depressive tendencies. Social support may therefore be a long-term protective factor from depression irrespective of personality characteristics, such as hostility and anger. 相似文献
53.
Katja A Puttonen Sárka Lehtonen Pasi Lampela Pekka T M?nnist? Atso Raasmaja 《Toxicology in vitro》2008,22(1):182-189
Cell viability studies are useful when screening novel drugs for the diseases that are related to either increased cell death or enhanced cell survival. There are numerous assays but the results that they produce are rarely unanimous. Here we compared the performance of (1) morphological microscopic assay with double DNA staining, (2) propidium iodide-digitonin assay, (3) MTT-assay, and (4) ATP-assay in human neuroblastoma (SH-SY5Y), rat glioma (C6), rabbit smooth muscle (SMC), Chinese hamster ovary (CHO) and monkey fibroblast cells (CV1-P) exposed to cytosine arabinoside (Ara-C) and 6-hydroxydopamine (6-OHDA). We found that neuronal SH-SY5Y cells were most sensitive to both toxins and the results in all viability tests correlated well. All the other cell lines were much more resistant, particularly to Ara-C but also to 6-OHDA. Toxicity of the compounds was best revealed by MTT and ATP assays, measuring the metabolic activity of the cells, and only occasionally by morphological observations or with the propidium iodide-digitonin assay which is based on the cell membrane integrity. In this research, Ara-C induced pure apoptosis whereas the toxicity type of 6-OHDA was dose-dependent. The use of several viability tests and cell lines is recommended when studying cell death, particularly apoptosis, and performance of antiapoptotic compounds. 相似文献
54.
Hyman E Kauraniemi P Hautaniemi S Wolf M Mousses S Rozenblum E Ringnér M Sauter G Monni O Elkahloun A Kallioniemi OP Kallioniemi A 《Cancer research》2002,62(21):6240-6245
Genetic changes underlie tumor progression and may lead to cancer-specific expression of critical genes. Over 1100 publications have described the use of comparative genomic hybridization (CGH) to analyze the pattern of copy number alterations in cancer, but very few of the genes affected are known. Here, we performed high-resolution CGH analysis on cDNA microarrays in breast cancer and directly compared copy number and mRNA expression levels of 13,824 genes to quantitate the impact of genomic changes on gene expression. We identified and mapped the boundaries of 24 independent amplicons, ranging in size from 0.2 to 12 Mb. Throughout the genome, both high- and low-level copy number changes had a substantial impact on gene expression, with 44% of the highly amplified genes showing overexpression and 10.5% of the highly overexpressed genes being amplified. Statistical analysis with random permutation tests identified 270 genes whose expression levels across 14 samples were systematically attributable to gene amplification. These included most previously described amplified genes in breast cancer and many novel targets for genomic alterations, including the HOXB7 gene, the presence of which in a novel amplicon at 17q21.3 was validated in 10.2% of primary breast cancers and associated with poor patient prognosis. In conclusion, CGH on cDNA microarrays revealed hundreds of novel genes whose overexpression is attributable to gene amplification. These genes may provide insights to the clonal evolution and progression of breast cancer and highlight promising therapeutic targets. 相似文献
55.
Katja A. Puttonen rka Lehtonen Atso Raasmaja Pekka T. Mnnist 《Toxicology in vitro》2006,20(8):1446-1454
We studied the ability of prolyl oligopeptidase (POP) inhibitors, Z-Pro-Prolinal and JTP-4819, to prevent translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and formation of reactive oxygen species (ROS), in 6-hydroxydopamine (6-OHDA) and cytosine arabinoside (Ara-C) treated monkey fibroblast (CV1-P) and human neuroblastoma (SH-SY5Y) cells. The cells were pretreated with POP inhibitors (30 min) before addition of toxicants. GAPDH was analyzed by Western hybridization, ROS by fluorescent 2′7′-dichlorodihydro-fluorescein diacetate, and viability by the MTT method. Both toxicants induced GAPDH translocation to the particulate fraction (mitochondria and nuclei). Z-Pro-Prolinal was able to inhibit the translocation in 6-OHDA-exposed CV1-P cells. In SH-SY5Y cells and in JTP-4819 pretreated cells, no prevention of translocation was seen. However, the intensity of GAPDH in cytosolic fraction increased. Both inhibitors blocked 6-OHDA-induced ROS-production to the control level in CV1-P but, not in SH-SY5Y cells, without affecting their viability. In conclusion, POP inhibitors are able to prevent certain cell stress related factors such as ROS production or GAPDH translocation. 相似文献
56.
57.
Kristian Ovaska Pia Lindberg Valtteri Häyry Pilvi Maliniemi Anu Lintulahti Miikka Korja Riku Kivisaari Samer Hussein Seppo Sarna Kirsi Niiranen Sampsa Hautaniemi Hannu Haapasalo Annamari Ranki 《Genes, chromosomes & cancer》2013,52(2):191-201
Copy number changes or reduced expression of the Neuron navigator 3 (NAV3) gene occurs in neuroblastomas and malignancies of epithelial or lymphoid origin. To elucidate whether NAV3 has a role in the tumorigenesis of nervous system tumors in general, we studied central and peripheral nervous system tumors for NAV3 copy number changes. In search for common tumorigenic denominators, we analyzed 113 central and peripheral nervous system tumors, including glial tumors (grades I–IV gliomas), medulloblastomas, and neuroblastomas. NAV3 copy number changes were studied by fluorescence in situ hybridization and correlated to survival analyses. To identify target genes of NAV3 deletion, NAV3 was silenced by siRNA in glioblastoma cell lines and gene expression profiles were analyzed by Agilent 4×44k dual‐color microarrays. Selected upregulations were confirmed by immunohistochemistry and quantitative polymerase chain reaction. We found NAV3 amplifications to dominate in neuronally differentiated tumors, whereas glial tumors showed almost equal proportions of NAV3 deletion and amplification. However, Grade IV gliomas had more frequent NAV3 deletions than grades I–III gliomas. Silencing of NAV3 in glioma cell lines led to the upregulation of receptor genes associated with gonadotropin‐releasing hormone and Jak‐Stat signaling pathways. Kaplan–Meier analysis of the entire clinical tumor material showed association between NAV3 amplifications and favorable prognosis, as well as NAV3 deletions and unfavorable prognosis. With Cox regression model, a hazard ratio of 0.51 was observed for NAV3 amplifications and 1.36 for NAV3 deletions. We conclude that NAV3 may be a potential new prognostic biomarker and a potential therapeutic target. © 2012 Wiley Periodicals, Inc. 相似文献
58.
Antti J. K. Väisänen Marko Hyttinen Sampsa Ylönen Lauri Alonen 《Journal of occupational and environmental hygiene》2019,16(3):258-271
The aim of this study was to measure the concentrations of gaseous and particulate contaminants originated from additive manufacturing operations and post-processes in an occupational setting when plastics were used as feedstock materials. Secondary aims were to evaluate the concentration levels based on proposed exposure limits and target values and to propose means to reduce exposure to contaminants released in additive manufacturing processes. Volatile organic compounds were sampled with Tenax TA adsorption tubes and analyzed with a thermo desorption gas chromatography-mass spectrometry instrument. Carbonyl compounds were sampled with DNPH-Silica cartridges and analyzed with a high-performance liquid chromatography device. Particles were measured with P-Trak instrument and indoor air quality was sampled with IAQ-Calc instrument. Dust mass concentrations were measured simultaneously with a DustTrak DRX instrument and IOM-samplers. Particle concentrations were highest (2070-81 890 #/cm3 mean) during manufacturing with methods where plastics were thermally processed. Total volatile organic compounds concentrations, in contrast, were low (113–317 µg/m3 mean) during manufacturing with such methods, and vat photopolymerization. However, total volatile organic compounds concentrations of material jetting and multi jet fusion methods were higher (1,114–2,496 µg/m3 mean), perhaps because of material and binder spraying, where part of the spray can become aerosolized. Chemical treatment of manufactured objects was found to be a severe volatile organic compounds source as well. Formaldehyde was detected in low concentrations (3–40 µg/m3) in all methods except for material jetting method, in addition to several other carbonyl compounds. Notable dust concentrations (1.4–9.1?mg/m3) were detected only during post-processing of powder bed fusion and multi jet fusion manufactured objects. Indoor air quality parameters were not found to be notably impacted by manufacturing operations. Only low concentrations (below 2?ppm) of CO were detected during several manufacturing processes. All studied additive manufacturing operations emitted potentially harmful contaminants into their environments, which should be considered in occupational additive manufacturing and workplace design. According to the measured contaminant levels it is possible that adverse additive manufacturing related health effects may occur among exposed workers. 相似文献
59.
Kirsi Palmu Turkka Kirjavainen Susanna Stjerna Tommi Salokivi Sampsa Vanhatalo 《Clinical neurophysiology》2013,124(9):1807-1814
ObjectiveTo document the occurrence of genuine sleep stages in the early preterm babies, and to develop an EEG-based index for following sleep wake cyclicity.MethodsTwelve preterm babies were recruited from a study that assessed ventilator strategies. We used altogether 18 polysomnography recordings that were collected at mean conceptional age of 29.3 (25.9–32.7) weeks. Spontaneous activity transients (SAT) were detected automatically and their cumulative coverage in each 20 s interval was computed from the EEG derivations C3–A2 and O2–A1. Mean SAT% values between sleep stages were compared.ResultsAll babies exhibited all sleep stages, however the sleep was remarkably fragmentary in infants due to their respiratory issues. The EEG index, SAT% showed temporal behavior that strikingly well compared with the sleep stage fluctuations in the hypnogram. In the statistical analysis we found significant differences in all recordings between the deep (quiet) sleep and the REM sleep.ConclusionGenuine sleep states exist in the early preterm babies, and changes in sleep stages are reflected in the EEG activity in a way that can be readily measured by assessing fluctuation of the automatically detected, EEG based index, the SAT%.SignificanceThe findings open a possibility to construct automated analysis or monitoring of sleep wake cyclicity into brain monitors in neonatal intensive care unit. 相似文献
60.
Katja Kaipio Ping Chen Pia Roering Kaisa Huhtinen Piia Mikkonen Päivi Östling Laura Lehtinen Naziha Mansuri Taina Korpela Swapnil Potdar Johanna Hynninen Annika Auranen Seija Grénman Krister Wennerberg Sampsa Hautaniemi Olli Carpén 《The Journal of pathology》2020,250(2):159-169
Poor chemotherapy response remains a major treatment challenge for high-grade serous ovarian cancer (HGSC). Cancer stem cells are the major contributors to relapse and treatment failure as they can survive conventional therapy. Our objectives were to characterise stemness features in primary patient-derived cell lines, correlate stemness markers with clinical outcome and test the response of our cells to both conventional and exploratory drugs. Tissue and ascites samples, treatment-naive and/or after neoadjuvant chemotherapy, were prospectively collected. Primary cancer cells, cultured under conditions favouring either adherent or spheroid growth, were tested for stemness markers; the same markers were analysed in tissue and correlated with chemotherapy response and survival. Drug sensitivity and resistance testing was performed with 306 oncology compounds. Spheroid growth condition HGSC cells showed increased stemness marker expression (including aldehyde dehydrogenase isoform I; ALDH1A1) as compared with adherent growth condition cells, and increased resistance to platinum and taxane. A set of eight stemness markers separated treatment-naive tumours into two clusters and identified a distinct subgroup of HGSC with enriched stemness features. Expression of ALDH1A1, but not most other stemness markers, was increased after neoadjuvant chemotherapy and its expression in treatment-naive tumours correlated with chemoresistance and reduced survival. In drug sensitivity and resistance testing, five compounds, including two PI3K-mTOR inhibitors, demonstrated significant activity in both cell culture conditions. Thirteen compounds, including EGFR, PI3K-mTOR and aurora kinase inhibitors, were more toxic to spheroid cells than adherent cells. Our results identify stemness markers in HGSC that are associated with a decreased response to conventional chemotherapy and reduced survival if expressed by treatment-naive tumours. EGFR, mTOR-PI3K and aurora kinase inhibitors are candidates for targeting this cell population. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献