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1.
Sneyd J. R.; Wright PMC.; Cross M.; Thompson P.; Voortman G.; Weideman M. M.; Andrews CJH.; Daniell C. J. 《British journal of anaesthesia》1997,79(4):427-432
Ten male volunteers received a 1-min i.v. infusion of a new water soluble
steroid anaesthetic agent, ORG 21465. Individuals received doses ranging
from 0.8 to 1.8 mg kg-1. All subjects experienced venous pain at the site
of injection; those receiving 1.0 mg kg-1 or more became anaesthetized.
There was no evidence of histamine release and apnoea did not occur.
Excitatory phenomena were observed in all subjects and were dose related;
no spikes were seen on the EEG. Pharmacokinetic analysis supported a
three-compartment (non-weight- related) model with compartmental volumes
V1, V2 and V3 of 4.31, 14.2 and 89.4 litre, respectively. Clearance from
the central compartment V1 was 1.55 litre min-1. Inter-compartmental
clearances Q1 and Q2 were 2.54 and 1.79 litre min-1. We found that ORG
21465 was an effective anaesthetic in humans. The relationship between
sedation, anaesthesia and excitation requires further exploration.
相似文献
2.
International Journal of Clinical Pharmacy - 相似文献
3.
Joost P. Bruijntjes C. Frieke Kuper Joke E. Robinson Henk-Jan Schuurman 《Clinical & developmental immunology》1993,3(2):113-122
The histology of epithelium-free areas in the subcapsular region of the thymus was
studied in Wistar rats. Lymphocytes in these areas were CD4/CD8 double-positive, TCR
α/β positive in low intensity, and in CD5 labeling either negative or positive in low
intensity. There was a high proliferative activity as assessed by bromodeoxyuridine
incorporation in vivo and detected by immunohistochemistry. Various macrophage
types were observed. They were either large and round to slightly dendritic, or small
and dendritic. Most large cells were positive for MHC Class II, and labeled by the
antimacrophage antibodies ED1 and ED2. A few cells were strongly positive for Sudan
black, Oil red O, nonspecific esterase, and acid phosphatase; they resembled the large
rounded macrophages in the corticomedullary zone, although their MHC Class II and
ED2 staining was more intense. A few cells showed features of tingible body
macrophages, as they contained cellular debris.Serial sections showed that epithelium-free areas run from the subcapsular area to
deep in the cortex, and often border the medulla. This opens the opportunity for
immature lymphocytes to move into the medulla and corticomedullary zone without
contacting and potential selection with cortical stromal elements other than
macrophages in the epithelium-free areas. In this case, the epithelium-free areas may
offer a separate intrathymic pathway for T lymphocytes. 相似文献
4.
den Hartigh J Voortman G van Oort WJ Weenen H Pinedo HM 《Journal of pharmaceutical and biomedical analysis》1985,3(5):417-423
A study to ascertain suitable conditions for handling biological samples from patients, treated with the antibiotic mitomycin C (MMC), with the objective of improving the accuracy and reliability of the determination is described. Situations frequently occurring in medical practice are simulated to optimize procedures for reliable and reproducible sampling, sample treatment and determination of MMC. Continuation of drug partitioning in whole blood after sampling can be prevented by immediate cooling in ice before the separation of plasma from cells. The adjustment of the pH of urine samples is shown to be particularly important since a low urinary pH causes decomposition of MMC; moreover, it may decrease extraction recovery. Furthermore, long-term exposure of samples to daylight induces drug decomposition. Frozen storage of plasma and urine samples for periods greater than 3 weeks is to be avoided as this results in a considerable drop in MMC concentration. Repeated cycles of freezing and thawing are shown to have no effect upon the analytical results (6 cycles tested). The analysis of extracts of biological samples may take place up to at least 24 h after their preparation without measurable loss of analyte. 相似文献
5.
Boersema Henk-Jan Hoekstra Tialda Abma Femke Brouwer Sandra 《Journal of occupational rehabilitation》2021,31(4):796-806
Journal of Occupational Rehabilitation - Purpose Inability to work fulltime is an important outcome in the assessment of workers applying for a disability benefit. However, limited knowledge is... 相似文献
6.
Joshua R Lewis Trudy Voortman John PA Ioannidis 《Journal of bone and mineral research》2021,36(2):219-226
A healthy diet is essential to attain genetically determined peak bone mass and maintain optimal skeletal health across the adult lifespan. Despite the importance of nutrition for bone health, many of the nutritional requirements of the skeleton across the lifespan remain underexplored, poorly understood, or controversial. With increasingly aging populations, combined with rapidly changing diets and lifestyles globally, one anticipates large increases in the prevalence of osteoporosis and incidence of osteoporotic fractures. Robust, transparent, and reproducible nutrition research is a cornerstone for developing reliable public health recommendations to prevent osteoporosis and osteoporotic fractures. However, nutrition research is often criticized or ignored by healthcare professionals due to the overemphasis of weak science, conflicting, confusing or implausible findings, industry interests, common misconceptions, and strong opinions. Conversely, spurious research findings are often overemphasized or misconstrued by the media or prominent figures especially via social media, potentially leading to confusion and a lack of trust by the general public. Recently, reforms of the broader discipline of nutrition science have been suggested and promoted, leading to new tools and recommendations to attempt to address these issues. In this perspective, we provide a brief overview of what has been achieved in the field on nutrition and bone health, focusing on osteoporosis and osteoporotic fractures. We discuss what we view as some of the challenges, including inherent difficulties in assessing diet and its change, disentangling complex interactions between dietary components and between diet and other factors, selection of bone-related outcomes for nutrition studies, obtaining evidence with more unbiased designs, and perhaps most importantly, ensuring the trust of the public and healthcare professionals. This perspective also provides specific recommendations and highlights new developments and future opportunities for scientists studying nutrition and bone health. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
7.
8.
Zhangling Chen Jean-Philippe Drouin-Chartier Yanping Li Megu Y. Baden JoAnn E. Manson Walter C. Willett Trudy Voortman Frank B. Hu Shilpa N. Bhupathiraju 《Diabetes care》2021,44(3):663
OBJECTIVEWe evaluated the associations between changes in plant-based diets and subsequent risk of type 2 diabetes.RESEARCH DESIGN AND METHODSWe prospectively followed 76,530 women in the Nurses’ Health Study (NHS) (1986–2012), 81,569 women in NHS II (1991–2017), and 34,468 men in the Health Professionals Follow-up Study (1986–2016). Adherence to plant-based diets was assessed every 4 years with the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs). We pooled results of the three cohorts using meta-analysis.RESULTSWe documented 12,627 cases of type 2 diabetes during 2,955,350 person-years of follow-up. After adjustment for initial BMI and initial and 4-year changes in alcohol intake, smoking, physical activity, and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest decrease (>10%) in PDI and hPDI over 4 years had a 12–23% higher diabetes risk in the subsequent 4 years (pooled HR, PDI 1.12 [95% CI 1.05, 1.20], hPDI 1.23 [1.16, 1.31]). Each 10% increment in PDI and hPDI over 4 years was associated with a 7–9% lower risk (PDI 0.93 [0.91, 0.95], hPDI 0.91 [0.87, 0.95]). Changes in uPDI were not associated with diabetes risk. Weight changes accounted for 6.0–35.6% of the associations between changes in PDI and hPDI and diabetes risk.CONCLUSIONSImproving adherence to overall and healthful plant-based diets was associated with a lower risk of type 2 diabetes, whereas decreased adherence to such diets was associated with a higher risk. 相似文献
9.
Martin Gotthardt Decio L. Eizirik Henk-Jan Aanstoot Olle Korsgren Dick Mul Frank Martin Marti Boss Tom J. P. Jansen Sanne A. M. van Lith Mijke Buitinga Olof Eriksson Miriam Cnop Maarten Brom 《Diabetologia》2018,61(12):2516-2519
In this issue of Diabetologia, Alavi and Werner ( https://doi.org/10.1007/s00125-018-4676-1) criticise the attempts to use positron emission tomography (PET) for in vivo imaging of pancreatic beta cells, which they consider as ‘futile’. In support of this strong statement, they point out the limitations of PET imaging, which they believe render beta cell mass impossible to estimate using this method. In our view, the Alavi and Werner presentation of the technical limitations of PET imaging does not reflect the current state of the art, which leads them to questionable conclusions towards the feasibility of beta cell imaging using this approach. Here, we put forward arguments in favour of continuing the development of innovative technologies enabling in vivo imaging of pancreatic beta cells and concisely present the current state of the art regarding putative technical limitations of PET imaging. Indeed, far from being a ‘futile’ effort, we demonstrate that beta cell imaging is now closer than ever to becoming a long-awaited clinical reality. 相似文献
10.
Henk-Jan Schuurman W. Slingerland Klaus Mennninger Miriam Ossevoort Jean-Claude Hengy Birgit Dorobek Jacky Vonderscher Jan Ringers Mamoun Odeh Margreet Jonker 《Transplant international》2001,14(5):320-328
In cynomolgus and rhesus monkeys, the dose-normalized exposure of cyclosporine administered orally as microemulsion preconcentrate
(Neoral) was lower than that upon intramuscular administration. For oral administration, mean values ( ± SD) of Cmax, 24-h area-under-the curve (AUC) and 24-h trough level, all normalized for a 1 mg/kg dose, were 20 ± 9 ng kg/mg ml, 210 ±
70 ng h kg/mg ml and 2.6 ± 0.9 ng kg/mg ml, respectively. For intramuscular administration, levels were about 5.5-fold, 9-fold
and 22-fold higher. Based on pharmacokinetic data, the efficacy of oral cyclosporine treatment (without any other immunosuppressant)
was evaluated in life-supporting cynomolgus monkey kidney allotransplantation. Rejection-free kidney allograft survival could
be achieved using oral cyclosporine monotherapy with average 24-h trough concentrations above 100 ng/ml during maintenance
treatment. Typically, daily oral doses of 100 mg/kg–150 mg/kg during the first two weeks post-transplantation, followed by
daily 30 mg/kg–100 mg/kg dose levels during subsequent maintenance can result in long-term allograft survival, with 24-h average
trough levels in individual animals during maintenance between 110 ng/ml and 700 ng/ml.
Received: 1 October 1997 Revised: 20 April 2001 Accepted: 7 June 2001 相似文献