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991.
Stuehler C Khanna N Bozza S Zelante T Moretti S Kruhm M Lurati S Conrad B Worschech E Stevanović S Krappmann S Einsele H Latgé JP Loeffler J Romani L Topp MS 《Blood》2011,117(22):5881-5891
T cell-mediated heterologous immunity to different pathogens is promising for the development of immunotherapeutic strategies. Aspergillus fumigatus and Candida albicans, the 2 most common fungal pathogens causing severe infections in immunocompromised patients, are controlled by CD4+ type 1 helper T (T(H)1) cells in humans and mice, making induction of fungus-specific CD4+ T(H)1 immunity an appealing strategy for antifungal therapy. We identified an immunogenic epitope of the A fumigatus cell wall glucanase Crf1 that can be presented by 3 common major histocompatibility complex class II alleles and that induces memory CD4+ T(H)1 cells with a diverse T-cell receptor repertoire that is cross-reactive to C albicans. In BALB/c mice, the Crf1 protein also elicits cross-protection against lethal infection with C albicans that is mediated by the same epitope as in humans. These data illustrate the existence of T cell-based cross-protection for the 2 distantly related clinically relevant fungal pathogens that may foster the development of immunotherapeutic strategies. 相似文献
992.
BACKGROUND: Alloantibodies directed against the human neutrophil alloantigen (HNA)‐3a are frequently implicated in severe and fatal transfusion‐related acute lung injury (TRALI). The HNA‐3a/3b system results from a single‐nucleotide exchange (461G>A; Arg154Gln) in the choline transporter‐like protein 2 gene. Genotyping may allow identification of blood donors at risk to develop HNA‐3a antibodies. STUDY DESIGN AND METHODS: A polymerase chain reaction using sequence‐specific primers (PCR‐SSP) for genotyping of HNA‐3a and ‐3b alleles was designed. Results of genotyping and phenotyping were compared in 40 randomly selected individuals and in blood donors and recipients of six TRALI cases associated with HNA‐3a antibodies. Phenotyping was performed by granulocyte immunofluorescence and granulocyte agglutination using typing sera for HNA‐3a and two recently found HNA‐3b–reactive sera. Immunogenicity of HNA‐3a was determined by the rate of HNA‐3a alloantibodies in HNA‐3b homozygous parous women. RESULTS: Genotyping and phenotyping results correlated to 100% and were in accordance with alloantibody formation and binding in HNA‐3a antibody associated TRALI cases. Gene frequencies of HNA‐3a and ‐3b were 0.792 and 0.207 in the German population with 64.1% homozygous individuals for the HNA‐3a allele, 5.5% for the HNA‐3b allele, and 30.4% heterozygous individuals, in accordance with the Hardy‐Weinberg equilibrium and the gene frequencies of 0.819 and 0.181 reported in 1964. Immunization rates were estimated to be of 7% for HNA‐3a and 0.5% for HNA‐3b. CONCLUSION: The PCR‐SSP method allows reliable determination of the HNA‐3a and ‐3b genotypes; approximately 7% of HNA‐3b homozygous women develop antibodies when exposed to the HNA‐3a antigen during pregnancy. 相似文献
993.
Nattermann J Vogel M Nischalke HD Danta M Mauss S Stellbrink HJ Baumgarten A Mayr C Bruno R Tural C Klausen G Clotet B Naumann U Lutz T Rausch M Schewe K Bienek B Haerter G Sauerbruch T Rockstroh JK Spengler U 《The Journal of infectious diseases》2011,203(5):595-601
Recently, a IL28B (rs 12979860) gene polymorphism was identified as a predictor for response to hepatitis C virus-specific treatment in human immunodeficiency virus (HIV)-uninfected and -infected patients with chronic hepatitis C. In an analysis of HIV-infected patients with acute hepatitis C, we found that the IL28B genotype was associated with serum levels of hepatitis C virus RNA, g-GT, and CD4 cell count. In contrast to HIV-infected patients with chronic hepatitis C, the IL28B genotype was not significantly associated with treatment response rates in patients with acute hepatitis C. Thus, effects of the IL28B single-nucleotide polymorphism may differ in HIV-infected patients with chronic and acute hepatitis C. 相似文献
994.
Tobias Forster Vanessa Rausch Yiyao Zhang Orkhan Isayev Katharina Heilmann Frank Schoensiegel Li Liu Michelle Nessling Karsten Richter Sabrina Labsch Clifford C. Nwaeburu Juergen Mattern Jury Gladkich Nathalia Giese Jens Werner Peter Schemmer Wolfgang Gross Martha M. Gebhard Clarissa Gerhauser Michael Schaefer Ingrid Herr 《Oncotarget》2014,5(6):1621-1634
The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been
associated with blocked gap junctional intercellular communication (GJIC) and the
presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is
responsible for a CSC phenotype in established and primary cancer cells and patient
tissue of PDA using interdisciplinary methods based in physiology, cell and molecular
biology, histology and epigenetics. Flux of fluorescent dyes and gemcitabine through
gap junctions (GJs) was intact in less aggressive cells but not in highly malignant
cells with morphological dysfunctional GJs. Among several connexins, only Cx43 was
expressed on the cell surface of less aggressive and GJIC-competent cells, whereas
Cx43 surface expression was absent in highly malignant, E-cadherin-negative and
GJIC-incompetent cells. The levels of total Cx43 protein and Cx43 phosphorylated at
Ser368 and Ser279/282 were high in normal tissue but low to absent in malignant
tissue. si-RNA-mediated inhibition of Cx43 expression in GJIC-competent cells
prevented GJIC and induced colony formation and the expression of stem cell-related
factors. The bioactive substance sulforaphane enhanced Cx43 and E-cadherin levels,
inhibited the CSC markers c-Met and CD133, improved the functional morphology of GJs
and enhanced GJIC. Sulforaphane altered the phosphorylation of several kinases and
their substrates and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced
CX43 expression. The sulforaphane-mediated expression of Cx43 was not correlated with
enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter
de-methylation, suggesting that posttranslational phosphorylation is the dominant
regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances
aggressiveness, whereas sulforaphane counteracts this process, and our findings
highlight dietary co-treatment as a viable treatment option for PDA. 相似文献
995.
Christoph Kahlert Maria Fiala Gabriel Musso Niels Halama Sophia Keim Massimiliano Mazzone Felix Lasitschka Mathieu Pecqueux Fee Klupp Thomas Schmidt Nuh Rahbari Sebastian Sch?lch Christian Pilarsky Alexis Ulrich Martin Schneider Juergen Weitz Moritz Koch 《Oncotarget》2014,5(24):12978-12989
Pancreatic cancer consists of a heterogenous bulk of tumor cells and stroma cells which contribute to tumor progression by releasing angiogenic factors. Those factors can be detected as circulating serum factors. We performed a compartment-specific analysis of tumor-derived and stroma-derived angiogenic factors to identify biomarkers and molecular targets for the treatment of pancreatic cancer. Kryo-frozen tissue from primary ductal adenocarcinomas (n = 51) was laser-microdissected to isolate tumor and stroma tissue. Expression of 17 angiogenic factors (angiopoietin-2, follistatin, GCSF, HGF, interleukin-8, leptin, PDGF-BB, PECAM-1, VEGF, matrix metalloproteinase -1, -2, -3, -7, -9, -10, -12, and -13) was analyzed using a multiplex elisa assay for tissue-derived proteins and corresponding serum.Our study reveals a compartment-specific expression profile for several angiogenic factors and matrix metalloproteinases. ROC analysis of corresponding serum samples reveals MMP-7 and MMP-12 as strong classifiers for the diagnosis of patients with pancreatic cancer vs. healthy control donors. High expression of tumor-derived PDGF-BB and MMP-1 correlates with prolonged survival in univariate and multivariate analysis. In conclusion, a distinct expression patterns for angiogenic cytokines and MMPs in pancreatic cancer and surrounding stroma may implicate them as novel targets for cancer treatment. Tumor-derived PDGF-BB and MMP-1 are significant and independent prognostic markers for poor survival. 相似文献
996.
Philipp Kickingereder Christina Hamisch Bogdana Suchorska Norbert Galldiks Veerle Visser-Vandewalle Roland Goldbrunner Martin Kocher Harald Treuer Juergen Voges Maximilian I. Ruge 《Journal of neuro-oncology》2014,120(3):615-623
Treatment options for inoperable glioblastoma are limited. Low-dose-rate stereotactic iodine-125 brachytherapy (SBT) has been reported as an effective and low-risk treatment option for circumscribed low-grade gliomas and brain metastases. The present study evaluates this treatment approach for patients with inoperable glioblastoma. Between 1990 and 2012, 201 patients with histologically proven glioblastoma were treated with SBT (iodine-125 seeds; median cumulative surface dose, 60 Gy; median dose-rate, 6 cGy/h; median gross-tumor-volume, 17 ml) either as primary treatment (n = 103) or at recurrence (n = 98). In addition to SBT, 90.3 % of patients in the primary treatment group received external boost radiotherapy (median dose, 25.2 Gy). Adjuvant chemotherapy was added for 30.8 % of patients following SBT and consisted of temozolomide for the majority of cases (88.7 %). Procedure-related complications, clinical outcome, progression-free and overall survival (PFS, OS) were evaluated. Median follow-up was 9.8 months. The procedure-related mortality was zero. During follow-up, transient and permanent procedure-related morbidity was observed in 7.5 and 2.0 %, respectively. Calculated from the time of SBT, median OS and PFS rates were 10.5 and 6.2 months, with no significant differences among primary and recurrent tumors (11.1 vs.10.4 months for OS and 6.2 vs. 5.9 months for PFS). For OS, multivariate analysis revealed Karnofsky performance score, age, and adjuvant chemotherapy as independent prognostic factors (all p < 0.01). Low-dose-rate SBT is a relatively safe and potentially effective local treatment option for patients with circumscribed inoperable glioblastoma initially or at recurrence. It deserves prospective validation since it may improve the outcome for a subset of patients with inoperable GBM. 相似文献
997.
Hartmut Meister Isabel Lausberg Juergen Kiessling Hasso von Wedel Martin Walger 《European archives of oto-rhino-laryngology》2002,259(10):531-534
Older patients represent the majority of hearing-aid users. The needs of elderly, hearing-impaired subjects are not entirely identified. The present study aims to determine the importance of fundamental hearing-aid attributes and to elicit the utility of associated hypothetical hearing aids for older patients. This was achieved using a questionnaire-based conjoint analysis--a decompositional approach to preference measurement offering a realistic study design. A random sample of 200 experienced hearing-aid users participated in the study. Though three out of the six examined attributes revealed age-related dependencies, the only significant effect was found for the attribute "handling", which was considerably more important for older than younger hearing-aid users. A trend of decreasing importance of speech intelligibility in noise and increasing significance of speech in quiet was observed for subjects older than 70 years. In general, the utility of various hypothetical hearing aids was similar for older and younger subjects. Apart from the attribute "handling", older and younger subjects have comparable needs regarding hearing-aid features. On the basis of the examined attributes, there is no requirement for hearing aids designed specifically for elderly hearing-aid users, provided that ergonomic features are considered and the benefits of modern technology are made fully available for older patients. 相似文献
998.
999.
Smesny S Langbein K Rzanny R Gussew A Burmeister HP Reichenbach JR Sauer H 《Schizophrenia Research》2012,138(2-3):164-170