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Elion Hoxha Sigrid Harendza Hans Pinnschmidt Ulf Panzer Rolf A.K. Stahl 《Clinical journal of the American Society of Nephrology》2014,9(11):1883-1890
Background and objectives
Loss of renal function in patients with primary membranous nephropathy cannot be reliably predicted by laboratory or clinical markers at the time of diagnosis. M-type phospholipase A2 receptor autoantibodies have been shown to be associated with changes in proteinuria. Their eventual effect on renal function, however, is unclear.Design, setting, participants, & measurements
In this prospective, open, multicenter study, the potential role of M-type phospholipase A2 receptor autoantibodies levels on the increase of serum creatinine in 118 consecutive patients with membranous nephropathy and positivity for serum M-type phospholipase A2 receptor autoantibodies was analyzed. Patients were included in the study between April of 2010 and December of 2012 and observed until December of 2013. The clinical end point was defined as an increase of serum creatinine by ≥25% and serum creatinine reaching ≥1.3 mg/dl.Results
Patients were divided into tertiles according to their M-type phospholipase A2 receptor autoantibody levels at the time of inclusion in the study: tertile 1 levels=20–86 units/ml (low), tertile 2 levels=87–201 units/ml (medium), and tertile 3 levels ≥202 units/ml (high). The median follow-up time of all patients in the study was 27 months (interquartile range=18–33 months). The clinical end point was reached in 69% of patients with high M-type phospholipase A2 receptor autoantibodies levels (tertile 3) but only 25% of patients with low M-type phospholipase A2 receptor autoantibodies levels. The average time to reach the study end point was 17.7 months in patients with high M-type phospholipase A2 receptor autoantibodies levels and 30.9 months in patients with low M-type phospholipase A2 receptor autoantibodies levels. A multivariate Cox regression analysis showed that high M-type phospholipase A2 receptor autoantibodies levels—in addition to men and older age—are an independent predictor for progressive loss of renal function.Conclusions
High M-type phospholipase A2 receptor autoantibodies levels were associated with more rapid loss of renal function in this cohort of patients with primary membranous nephropathy and therefore, could be helpful for treatment decisions. 相似文献23.
Rachael O. Forsythe Jan Apelqvist Edward J. Boyko Robert Fitridge Joon Pio Hong Konstantinos Katsanos Joseph L. Mills Sigrid Nikol Jim Reekers Maarit Venermo R. Eugene Zierler Nicolaas C. Schaper Robert J. Hinchliffe 《Diabetes/metabolism research and reviews》2020,36(Z1)
The accurate identification of peripheral artery disease (PAD) in patients with diabetes and foot ulceration is important, in order to inform timely management and to plan intervention including revascularisation. A variety of non‐invasive tests are available to diagnose PAD at the bedside, but there is no consensus as to the most useful test, or the accuracy of these bedside investigations when compared to reference imaging tests such as magnetic resonance angiography, computed tomography angiography, digital subtraction angiography or colour duplex ultrasound. Members of the International Working Group of the Diabetic Foot updated our previous systematic review, to include all eligible studies published between 1980 and 2018. Some 15 380 titles were screened, resulting in 15 eligible studies (comprising 1563 patients, of which >80% in each study had diabetes) that evaluated an index bedside test for PAD against a reference imaging test. The primary endpoints were positive likelihood ratio (PLR) and negative likelihood ratio (NLR). We found that the most commonly evaluated test parameter was ankle brachial index (ABI) <0.9, which may be useful to suggest the presence of PAD (PLR 6.5) but an ABI value between 0.9 and 1.3 does not rule out PAD (NLR 0.31). A toe brachial index >0.75 makes the diagnosis of PAD less likely (NLR 0.14‐0.24), whereas pulse oximetry may be used to suggest the presence of PAD (if toe saturation < 2% lower than finger saturation; PLR 17.23‐30) or render PAD less likely (NLR 0.2‐0.27). We found that the presence of triphasic tibial waveforms has the best performance value for excluding a diagnosis of PAD (NLR 0.09‐0.28), but was evaluated in only two studies. In addition, we found that beside clinical examination (including palpation of foot pulses) cannot reliably exclude PAD (NLR 0.75), as evaluated in one study. Overall, the quality of data is generally poor and there is insufficient evidence to recommend one bedside test over another. While there have been six additional publications in the last 4 years that met our inclusion criteria, more robust evidence is required to achieve consensus on the most useful non‐invasive bedside test to diagnose PAD. 相似文献
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25.
Joyce M.G. Florisson Irene M.J. Mathijssen Belinda Dumee Jeannette A.M. Hoogeboom Pino J. Poddighe Ben A. Oostra Jean Pierre Frijns Linda Koster Annelies de Klein Bert Eussen Bert B.A. de Vries Sigrid Swagemakers Peter J. van der Spek Annemieke J.M.H. Verkerk PhD 《American journal of medical genetics. Part A》2013,161(2):244-253
In a screening project of patients with (complex) craniosynostosis using genomic arrays, we identified two patients with craniosynostosis and microcephaly with a deletion in the 2p15p16.1 chromosomal region. This region has been associated with a new microdeletion syndrome, for which patients have various features in common, including microcephaly and intellectual disability. Deletions were identified using Affymetrix 250K SNP array and further characterized by fluorescence in situ hybridization (FISH) analysis and qPCR. The deletions in our two patients overlapped within the 2p15p16.1 microdeletion syndrome area and were 6.8 and 6.9 Mb in size, respectively. FISH and qPCR confirmed the presence of only one copy in this region. Finemapping of the breakpoints indicated precise borders in our patients and were further finemapped in two other previously reported patients. Clinical features of patients with deletions in the 2p15p16.1 region vary. Including data from our patients, now eight out of nine reported patients have microcephaly, one of the major features, and all had intellectual disability. The current reported two patients add different forms of craniosynostosis to the clinical spectrum of this recently recognized microdeletion syndrome. © 2013 Wiley Periodicals, Inc. 相似文献
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27.
Sigrid Carlsson Alexandra Maschino Fritz Schröder Chris Bangma Ewout W. Steyerberg Theo van der Kwast Geert van Leenders Andrew Vickers Hans Lilja Monique J. Roobol 《European urology》2013
Background
Treatment decisions can be difficult in men with low-risk prostate cancer (PCa).Objective
To evaluate the ability of a panel of four kallikrein markers in blood—total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2—to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries.Design, setting, and participants
The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA ≥3.0 ng/ml and were treated with RP between 1994 and 2004.Outcome measurements and statistical analysis
We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3–T4, extracapsular extension, tumor volume >0.5 cm3, or any Gleason grade ≥4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood.Results and limitations
A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p < 0.0005). The model retained its ability in patients with low-risk and very-low-risk disease and in comparison with the Steyerberg nomogram, a published prediction model. Clinical application of the model incorporating the kallikrein markers would reduce rates of surgery by 135 of 1000 patients overall and 110 of 334 patients with pathologically insignificant disease. A limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model.Conclusions
Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment. 相似文献28.
Heleen Westland Yvonne Koop Carin D. Schröder Marieke J. Schuurmans P. Slabbers Jaap C. A. Trappenburg Sigrid C. J. M. Vervoort 《BMC family practice》2018,19(1):194
Background
Self-management support is widely accepted for the management of chronic conditions. Self-management often requires behaviour change in patients, in which primary care nurses play a pivotal role. To support patients in changing their behaviour, the structured behaviour change Activate intervention was developed. This intervention aims to enhance physical activity in patients at risk for cardiovascular disease in primary care as well as to enhance nurses’ role in supporting these patients. This study aimed to evaluate nurses’ perceptions towards the delivery and feasibility of the Activate intervention.Methods
A qualitative study nested within a cluster-randomised controlled trial using semistructured interviews was conducted and thematically analysed. Fourteen nurses who delivered the Activate intervention participated.Results
Three key themes emerged concerning nurses’ perceptions of delivering the intervention: nurses’ engagement towards delivering the intervention; acquiring knowledge and skills; and dealing with adherence to the consultation structure. Three key themes were identified concerning the feasibility of the intervention: expectations towards the use of the intervention in routine practice; perceptions towards the feasibility of the training programme; and enabling personal development.Conclusions
Delivering a behaviour change intervention is challenged by the complexity of changing nurses’ consultation style, including acquiring corresponding knowledge and skills. The findings have increased the understanding of the effectiveness of the Activate trial and will guide the development and evaluation of future behaviour change interventions delivered by nurses in primary care.Trial registration
ClinicalTrials.gov NCT02725203.29.
Leishmania donovani polyamine biosynthetic enzyme overproducers as tools to investigate the mode of action of cytotoxic polyamine analogs 下载免费PDF全文
Roberts SC Jiang Y Gasteier J Frydman B Marton LJ Heby O Ullman B 《Antimicrobial agents and chemotherapy》2007,51(2):438-445
A number of anticancer and antiparasitic drugs are postulated to target the polyamine biosynthetic pathway and polyamine function, but the exact mode of action of these compounds is still being elucidated. To establish whether polyamine analogs specifically target enzymes of the polyamine pathway, a model was developed using strains of the protozoan parasite Leishmania donovani that overproduce each of the polyamine biosynthetic enzymes. Promastigotes overexpressing episomal constructs encoding ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (ADOMETDC), or spermidine synthase (SPDSYN) revealed robust overproduction of the corresponding polyamine biosynthetic enzyme. Polyamine pools, however, were either unchanged or only marginally affected, implying that regulatory mechanisms must exist. The ODC, ADOMETDC, and SPDSYN overproducer strains exhibited a high level of resistance to difluoromethylornithine, 5'-{[(Z)-4-amino-2-butenyl]methylamino}-5'-deoxyadenosine, and n-butylamine, respectively, confirming previous observations that these agents specifically target polyamine enzymes. Conversely, augmented levels of polyamine biosynthetic enzymes did not affect the sensitivity of L. donovani promastigotes to pentamidine, berenil, and mitoguazone, drugs that were postulated to target the polyamine pathway, implying alternative and/or additional targets for these agents. The sensitivities of wild-type and overproducing parasites to a variety of polyamine analogs were also tested. The polyamine enzyme-overproducing lines offer a rapid cell-based screen for assessing whether synthetic polyamine analogs exert their mechanism of action predominantly on the polyamine biosynthetic pathway in L. donovani. Furthermore, the drug resistance engendered by the amplification of target genes and the overproduction of the encoded protein offers a general strategy for evaluating and developing therapeutic agents that target specific proteins in Leishmania. 相似文献
30.
OBJECTIVES: The composition of the extracellular matrix (ECM) plays a substantial role in bone remodelling, fracture healing and osseointegration of dental implants by regulating proliferation, migration and finally differentiation of osteogenic cell populations. Emdogain, a composition of an enamel matrix derivative (EMD), has been introduced as a potential candidate to promote tissue regeneration. We investigated whether EMD could serve as a potential promoter of cell proliferation and motility as a dynamic cell response and compared the results with the ubiquitous single ECM components type I collagen and laminin. MATERIAL AND METHODS: In the investigation presented, we used a continuous observation method for the analysis of migratory and proliferative patterns of individual cells. We analyzed the response of four osteoblastic cell lines to specific extracellular ligands (type I collagen, laminin and EMD) over a period of 24 h compared with untreated glass surface and bovine serum albumin (BSA) as control groups. RESULTS: Type I collagen and laminin promoted cell motility significantly compared with the control groups and, in part, compared with EMD as well. The analysis of all 451 investigated cells revealed the following mean values for cell motiliy: untreated glass (n=99): 5.46+/-2.74 microm/h, BSA (n=89): 6.35+/-2.43 microm/h, type I collagen (n=108): 8.77+/-3.42 microm/h, laminin (n=74): 9.89+/-5.10 microm/h and EMD (n=81): 7.92+/-3.35 microm/h. Proliferation rates on the different surfaces were heterogenous for all investigated cell lines and varied from 0% to 50% within 24 h without a correlation to cell motility. CONCLUSION: In our study, EMD promotes cell motility better than the control groups. The two investigated single ECM components type I collagen and laminin promoted cell motility superior to EMD. This supports the hypothesis that EMD promotes a less mobile but more differentiated osteogenic phenotype. 相似文献