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排序方式: 共有1111条查询结果,搜索用时 78 毫秒
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Leonie Konczalla Daniel R. Perez Nadine Wenzel Gerrit Wolters-Eisfeld Clarissa Klemp Johanna Lüddeke Annika Wolski Dirk Landschulze Chris Meier Anika Buchholz Dichao Yao Bianca T. Hofmann Julia K. Graß Sarah L. Spriestersbach Katharina Grupp Udo Schumacher Christian Betzel Svetlana Kapis Theresa Nuguid Pablo Steinberg Klaus Püschel Guido Sauter Maximillian Bockhorn Faik G. Uzunoglu Jakob R. Izbicki Cenap Güngör Alexander T. El Gammal 《International journal of cancer. Journal international du cancer》2020,146(6):1618-1630
MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms. 相似文献
3.
Brand Fabian Dendler Leonie Fiack Suzan Schulze Annett Böl Gaby-Fleur 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2022,65(5):599-607
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Regulierungswissenschaftliche Organisationen wie das Bundesinstitut für Risikobewertung (BfR) sehen sich in ihrer... 相似文献
4.
Dinja T. Kruger Xanthippi Alexi Mark Opdam Karianne Schuurman Leonie Voorwerk Joyce Sanders Vincent van der Noort Epie Boven Wilbert Zwart Sabine C. Linn 《International journal of cancer. Journal international du cancer》2020,146(8):2348-2359
Preclinical studies indicate that activated IGF-1R can drive endocrine resistance in ER-positive (ER+) breast cancer, but its clinical relevance is unknown. We studied the effect of IGF-1R signaling on tamoxifen benefit in patients and we searched for approaches to overcome IGF-1R-mediated tamoxifen failure in cell lines. Primary tumor blocks from postmenopausal ER+ breast cancer patients randomized between adjuvant tamoxifen versus nil were recollected. Immunohistochemistry for IGF-1R, p-IGF-1R/InsR, p-ERα(Ser118), p-ERα(Ser167) and PI3K/MAPK pathway proteins was performed. Multivariate Cox models were employed to assess tamoxifen efficacy. The association between p-IGF-1R/InsR and PI3K/MAPK pathway activation in MCF-7 and T47D cells was analyzed with Western blots. Cell proliferation experiments were performed under various growth-stimulating and -inhibiting conditions. Patients with ER+, IGF-1R-positive breast cancer without p-IGF-1R/InsR staining (n = 242) had tamoxifen benefit (HR 0.41, p = 0.0038), while the results for p-IGF-1R/InsR-positive patients (n = 125) were not significant (HR 0.95, p = 0.3). High p-ERα(Ser118) or p-ERα(Ser167) expression was associated with less tamoxifen benefit. In MCF-7 cells, IGF-1R stimulation increased phosphorylation of PI3K/MAPK proteins and ERα(Ser167) regardless of IGF-1R overexpression. This could be abrogated by the dual IGF-1R/InsR inhibitor linsitinib, but not by the IGF-IR-selective antibody 1H7. In MCF-7 and T47D cells, stimulation of the IGF-1R/InsR pathway resulted in cell proliferation regardless of tamoxifen. Abrogation of cell growth was regained by addition of linsitinib. In conclusion, p-IGF-1R/InsR positivity in ER+ breast cancer is associated with reduced benefit from adjuvant tamoxifen in postmenopausal patients. In cell lines, stimulation rather than overexpression of IGF-1R is driving tamoxifen resistance to be abrogated by linsitinib. 相似文献
5.
The Clostridium botulinum C3 exoenzyme selectively ADP-ribosylates low molecular weight GTP-binding proteins RhoA, B and C. This covalent modification inhibits Rho signaling activity, resulting in distinct actin cytoskeleton changes. Although C3 exoenzyme has no binding, the translocation domain assures that C3 enters cells and acts intracellularly. C3 uptake is thought to occur due to the high concentration of the C3 enzyme. However, recent work indicates that C3 is selectively endocytosed, suggesting a specific endocytotic pathway, which is not yet understood. In this study, we show that the C3 exoenzyme binds to cell surfaces and is internalized in a time-dependent manner. We show that the intermediate filament, vimentin, is involved in C3 uptake, as indicated by the inhibition of C3 internalization by acrylamide, a known vimentin disruption agent. Inhibition of C3 internalization was not observed by chemical inhibitors, like bafilomycin A, methyl-β-cyclodextrin, nocodazole or latrunculin B. Furthermore, the internalization of C3 exoenzyme was markedly inhibited in dynasore-treated HT22 cells. Our results indicate that C3 internalization depends on vimentin and does not depend strictly on both clathrin and caveolae. 相似文献
6.
Pauline A. J. Mendelaar Jaco Kraan Mai Van Leonie L. Zeune Leon W. M. M. Terstappen Esther Oomende Hoop John W. M. Martens Stefan Sleijfer 《Molecular oncology》2021,15(1):116
Circulating tumor cells (CTCs) in the blood of cancer patients are of high clinical relevance. Since detection and isolation of CTCs often rely on cell dimensions, knowledge of their size is key. We analyzed the median CTC size in a large cohort of breast (BC), prostate (PC), colorectal (CRC), and bladder (BLC) cancer patients. Images of patient‐derived CTCs acquired on cartridges of the FDA‐cleared CellSearch® method were retrospectively collected and automatically re‐analyzed using the accept software package. The median CTC diameter (μm) was computed per tumor type. The size differences between the different tumor types and references (tumor cell lines and leukocytes) were nonparametrically tested. A total of 1962 CellSearch® cartridges containing 71 612 CTCs were included. In BC, the median computed diameter (CD) of patient‐derived CTCs was 12.4 μm vs 18.4 μm for cultured cell line cells. For PC, CDs were 10.3 μm for CTCs vs 20.7 μm for cultured cell line cells. CDs for CTCs of CRC and BLC were 7.5 μm and 8.6 μm, respectively. Finally, leukocytes were 9.4 μm. CTC size differed statistically significantly between the four tumor types and between CTCs and the reference data. CTC size differences between tumor types are striking and CTCs are smaller than cell line tumor cells, whose size is often used as reference when developing CTC analysis methods. Based on our data, we suggest that the size of CTCs matters and should be kept in mind when designing and optimizing size‐based isolation methods.
Abbreviations
- ACCEPT
- Automated CTC Classification, Enumeration, and PhenoTyping software
- BC
- breast cancer
- BLC
- bladder cancer
- CD
- computed diameter
- CEL
- cultured tumor cell (cell line)
- CK
- cytokeratin
- CRC
- colorectal cancer
- CTC‐L
- circulating tumor cells derived from cerebrospinal fluid (liquor)
- CTCs
- circulating tumor cells
- DAPI
- 4′6‐diamidino‐2‐phenylindole
- EMT
- epithelial–mesenchymal transition
- EpCAM
- epithelial cell adhesion molecule
- IQR
- interquartile range
- KW test
- Kruskal–Wallis test
- MWU test
- Mann–Whitney U test
- NCR
- nucleus/cytoplasm ratio
- P2A
- perimeter to area
- PC
- prostate cancer
- TIF
- tagged Image Format files
- TXT
- text file
- μm
- micrometer
- µm2
- square micrometers
7.
Titus Josef Brinker Fabian Buslaff Caelán Haney Benedikt Gaim Ailís Ceara Haney Selina Marisa Schmidt Marc Phillipp Silchmüller Lava Taha Lena Jakob Hannah Maria Baumert Marvin Hallmann Marlene Heckl Jonas Alfitian Christian Martin Brieske Evgenia Petrova Divizieva Jilada Wilhelm Gabriel Hillebrand Dominik Penka Sanjeevan Raveendranathan Netzwerk Aufklärung gegen Tabak Janina Leonie Suhre 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2018,61(11):1453-1461
Smoking is the leading preventable cause of premature death in Germany. The network “Education Against Tobacco” (EAT) is an initiative that was founded in Germany in 2012, in which more than 3500 medical students and physicians engage in volunteer work in about 80 medical faculties in 14 countries. In this article, the concept, activities, objectives and associated research studies oft he EAT initiative are introduced.On the school level, the initiative addresses 10- to 15-year-old secondary school students. In addition to a multimodal approach, school visits use modern media such as facemorphing apps, which are not only used by students (45,000 per year in 14 countries), but by a total of over 500,000 other people as well. The effectiveness of the school-based intervention is currently being investigated in randomised long-term studies with 20,000 adolescents in Germany. A first long-term study demonstrated evidence of a protective effect regarding the onset of smoking, especially among female students, students having a low level of education and students with a migratory background.The programme educates several hundred prospective physicians at 13 (of 28 participating) German medical faculties each year in science-based elective courses for the well-established smoking cessation counselling of patients and sensitises them to the tobacco epidemic. The approved members engage in dialogue with local members of the German house of representatives as “Ärzteverband Tabakprävention”.EAT motivates the prospective generation of physicians, initially through prevention in school settings, to face the challenge of national tobacco control at the university and federal level. 相似文献
8.
Klaufus Leonie H. Fassaert Thijs J. L. de Wit Matty A. S. 《Social psychiatry and psychiatric epidemiology》2014,49(7):1139-1149
Social Psychiatry and Psychiatric Epidemiology - This study explored (in)equities between ethnic groups in the Netherlands regarding their access to health care for symptoms of common mental... 相似文献
9.
Oldmeadow LB McBurney H Robertson VJ Kimmel L Elliott B 《Archives of physical medicine and rehabilitation》2004,85(9):1424-1427
OBJECTIVE: To determine whether targeted postoperative care, based on preoperative risk assessment, can increase the number of patients who are discharged home directly from acute care after elective hip or knee arthroplasty. DESIGN: Quasiexperimental with historical control. SETTING: A public university teaching hospital. PARTICIPANTS: One hundred patients who had an elective hip or knee arthroplasty. INTERVENTIONS: Between January and July 2001, 50 patients had their risk of discharge to extended inpatient rehabilitation assessed preoperatively with a newly developed Risk Assessment and Prediction Tool (RAPT). Postoperative management was targeted on the basis of the identified level of risk. Results were compared with those of a similar group of 50 patients treated between January and July 2000. MAIN OUTCOME MEASURES: Discharge destination, length of stay (LOS), and readmission rates. RESULTS: The percentage of patients discharged directly home increased significantly, from 34% during 2000 to 64% in 2001 (P=.002), with no increase in readmission rates in the 12 months postdischarge. In addition, the mean acute hospital LOS decreased by 1.1 days to 7.5 days in 2001 (P=.02). CONCLUSIONS: Use of the RAPT and targeted postoperative care resulted in more patients being discharged directly home after hip or knee arthroplasty while hospital LOS further decreased. 相似文献
10.