全文获取类型
收费全文 | 729篇 |
免费 | 53篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 20篇 |
妇产科学 | 13篇 |
基础医学 | 150篇 |
口腔科学 | 124篇 |
临床医学 | 38篇 |
内科学 | 142篇 |
皮肤病学 | 3篇 |
神经病学 | 65篇 |
特种医学 | 11篇 |
外科学 | 51篇 |
一般理论 | 1篇 |
预防医学 | 53篇 |
眼科学 | 4篇 |
药学 | 22篇 |
肿瘤学 | 86篇 |
出版年
2022年 | 9篇 |
2021年 | 9篇 |
2020年 | 10篇 |
2019年 | 15篇 |
2018年 | 17篇 |
2017年 | 13篇 |
2016年 | 15篇 |
2015年 | 12篇 |
2014年 | 12篇 |
2013年 | 21篇 |
2012年 | 29篇 |
2011年 | 38篇 |
2010年 | 24篇 |
2009年 | 14篇 |
2008年 | 23篇 |
2007年 | 25篇 |
2006年 | 18篇 |
2005年 | 22篇 |
2004年 | 24篇 |
2003年 | 23篇 |
2002年 | 18篇 |
2001年 | 19篇 |
2000年 | 27篇 |
1999年 | 28篇 |
1998年 | 14篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1995年 | 9篇 |
1994年 | 9篇 |
1993年 | 8篇 |
1992年 | 19篇 |
1991年 | 15篇 |
1990年 | 27篇 |
1989年 | 15篇 |
1988年 | 29篇 |
1987年 | 19篇 |
1986年 | 23篇 |
1985年 | 16篇 |
1984年 | 17篇 |
1983年 | 7篇 |
1980年 | 4篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1977年 | 10篇 |
1976年 | 4篇 |
1975年 | 7篇 |
1972年 | 5篇 |
1971年 | 7篇 |
1968年 | 3篇 |
1966年 | 4篇 |
排序方式: 共有785条查询结果,搜索用时 31 毫秒
1.
E. Niclas Jonsson Rujia Xie Scott F. Marshall Rosalin H. Arends 《British journal of clinical pharmacology》2016,81(4):688-699
AimsThe aims were to 1) develop the pharmacokinetics model to describe and predict observed tanezumab concentrations over time, 2) test possible covariate parameter relationships that could influence clearance and distribution and 3) assess the impact of fixed dosing vs. a dosing regimen adjusted by body weight.MethodsIndividual concentration–time data were determined from 1608 patients in four phase 3 studies conducted to assess efficacy and safety of intravenous tanezumab. Patients received two or three intravenous doses (2.5, 5 or 10 mg) every 8 weeks. Blood samples for assessment of tanezumab PK were collected at baseline, 1 h post‐dose and at weeks 4, 8, 16 and 24 (or early termination) in all studies. Blood samples were collected at week 32 in two studies. Plasma samples were analyzed using a sensitive, specific, validated enzyme‐linked immunosorbent assay.ResultsA two compartment model with parallel linear and non‐linear elimination processes adequately described the data. Population estimates for clearance (CL), central volume (V
1), peripheral volume (V
2), inter‐compartmental clearance, maximum elimination capacity (VM) and concentration at half‐maximum elimination capacity were 0.135 l day–1, 2.71 l, 1.98 l, 0.371 l day–1, 8.03 μg day–1 and 27.7 ng ml–1, respectively. Inter‐individual variability (IIV) was included on CL, V
1, V
2 and VM. A mixture model accounted for the distribution of residual error. While gender, dose and creatinine clearance were significant covariates, only body weight as a covariate of CL, V
1 and V
2 significantly reduced IIV.ConclusionsThe small increase in variability associated with fixed dosing is consistent with other monoclonal antibodies and does not change risk : benefit. 相似文献
2.
Weiyu Ye Anna Olsson-Brown Robert A. Watson Vincent T. F. Cheung Robert D. Morgan Isar Nassiri Rosalin Cooper Chelsea A. Taylor Umair Akbani Oliver Brain Rubeta N. Matin Nicholas Coupe Mark R. Middleton Mark Coles Joseph J. Sacco Miranda J. Payne Benjamin P. Fairfax 《British journal of cancer》2021,124(10):1661
Background Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10−6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma 相似文献
3.
The difficulty of diagnosing NCSE in clinical practice; external validation of the Salzburg criteria
Rianne J. M. Goselink Jeroen J. van Dillen Marjolein Aerts Johan Arends Charlotte van Asch Inge van der Linden Jaco Pasman Christiaan G. J. Saris Machiel Zwarts Nens van Alfen 《Epilepsia》2019,60(8):e88-e92
To improve the diagnostic accuracy of electroencephalography (EEG) criteria for nonconvulsive status epilepticus (NCSE), external validation of the recently proposed Salzburg criteria is paramount. We performed an external, retrospective, diagnostic accuracy study of the Salzburg criteria, using EEG recordings from patients with and without a clinical suspicion of having NCSE. Of the 191 EEG recordings, 12 (12%) was classified as an NCSE according to the reference standard. In the validation cohort, sensitivity was 67% and specificity was 89%. The positive predictive value was 47% and the negative predictive value was 95%. Ten patients in the control group (n = 93) were false positive, resulting in a specificity of 89.2%. The interrater agreement between the reference standards and between the scorers of the Salzburg criteria was moderate; disagreement occurred mainly in patients with an epileptic encephalopathy. The Salzburg criteria showed a lower diagnostic accuracy in our external validation study than in the original design, suggesting that they cannot replace the current practice of careful weighing of both clinical and EEG information on an individual basis. 相似文献
4.
J Arends J Christoffersen M R Christoffersen B Ogaard A G Dijkman W L Jongebloed 《Caries research》1992,26(1):18-21
In this paper, data are presented on the in situ demineralization of human enamel as a function of the demineralization period. To quantify the mineral loss parameters versus time, it is important to obtain information on the kinetics, and thus on the mechanism of dental caries. The results show that for in situ enamel demineralization, the lesion depth as well as the mineral loss parameter both vary linearly with the demineralization time. This is in contrast to in vitro lesion formation where the third power, or the square power of the lesion depth is linearly related to the demineralization time. In in situ demineralization, the rate-determining step of the demineralization process is the inhibitor-controlled dissolution process at the enamel crystallite surfaces, while the inhibitor content (F-, proteins etc.) in the lesion originating from the plaque, saliva and enamel is high. Furthermore, the study indicates that in in situ demineralization, interprismatic mineral loss is very important. 相似文献
5.
Ohne Zusammenfassung 相似文献
6.
Rianne P Reijs Saskia G M van Mil Mariette H J A van Hall Johan B A M Arends Jacobiene W Weber Willy O Renier Albert P Aldenkamp 《Seizure》2007,16(5):438-444
INTRODUCTION: One-third of children with epilepsy are classified as having a cryptogenic localization related epilepsy (CLRE). In cohort studies CLRE is often grouped together with either symptomatic localization related epilepsy (SLRE) or idiopathic generalized epilepsy (IGE). Therefore, this categorization is not specific enough and will not lead to prognostic or treatment information. We objectified the classification differences between these categories. METHODS: A total of 114 children admitted to our epilepsy centre underwent a standardized clinical analysis, which yielded age at onset, duration of the epilepsy, seizure frequency, seizure type, percentage of interictal epileptiform activity on EEG (IEA), type of treatment, and full scale IQ. These variables are regarded the characteristics of the epilepsy, and used in a discriminant function analysis. RESULTS: IEA was found to be the only variable to distinguish between groups of epilepsy. SLRE could easily be distinguished significantly from IGE and CLRE, while the latter two did not differ significantly. Discriminant function analysis combined the variables into two functions, applicable to classify the children. By applying this statistical analysis method, the groups clinically classified as SLRE and IGE were mostly classified as SLRE (71.4%) and IGE (57.9%). However, CLRE appeared difficult to classify (49.2%), and most children were classified as either SLRE (19%) or IGE (31.7%). CONCLUSION: The current opinion that CLRE is 'probably symptomatic' cannot be confirmed in all cases in this study. It is most likely that the current CLRE population consists of both children with eventually SLRE, as well as yet to be described syndromes to be classified as idiopathic epilepsies. We emphasize the need for separate studies regarding children with 'probably symptomatic' (cryptogenic) localization related epilepsy, as this will maximally help children, caretakers and treating physicians to achieve the best possible outcome. 相似文献
7.
Lenka A. Taylor Jann Arends Arwen K. Hodina Clemens Unger Ulrich Massing 《Lipids in health and disease》2007,6(1):17
Background
It has been observed that ras-transformed cell lines in culture have a higher phosphatidylcholine (PC) biosynthesis rate as well as higher PC-degradation rate (increased PC-turnover) than normal cells. In correspondence to these findings, the concentrations of the PC-degradation product lyso-phosphatidylcholine (LPC) in cancer patients were found to be decreased. Our objective was the systematic investigation of the relationship between LPC and inflammatory and nutritional parameters in cancer patients. Therefore, plasma LPC concentrations were assessed in 59 cancer patients and related to nutritional and inflammatory parameters. To determine LPC in blood plasma we developed and validated a HPTLC method. 相似文献8.
F F de Mul M H Hottenhuis P Bouter J Greve J Arends J J ten Bosch 《Journal of dental research》1986,65(3):437-440
Using a Raman microspectrometer, we have recorded Raman spectra of synthetically produced hydroxyapatite samples with varying carbonate contents. The apatites were produced from aqueous solutions at about 40 degrees C. From line-broadening values of the symmetric phosphate stretch, it was concluded that the carbonate substitution in these lattices has a maximum of 4.5 wt %. Both phosphate and hydroxyl ions seem to be involved in the carbonate substitution process. 相似文献
9.
Sixteen cases of histopathologically proved solitary rectal ulcer syndrome were encountered. Fifteen patients underwent barium enema study; in nine cases the findings--including rectal stricture, granularity of the mucosa, and thickened rectal folds-were nonspecific. In six cases the study was normal. All patients had a long history of defecation disorders, and defecography was performed in all. In seven cases, intussusception of the rectal wall was seen; in another case the intussusception was accompanied by a rectocele. One case showed rectal prolapse. In four cases, failed relaxation of the puborectalis occurred and prevented the passage of the bolus; in another case there was abnormal perineal descent. In two patients studies were normal. In patients with defecation disorders, the possibility of this syndrome should be considered. Defecography is the method of choice for establishing the diagnosis. 相似文献
10.
The prevalence of anti-Helicobacter (Campylobacter) pylori antibodies in patients and healthy blood donors 总被引:2,自引:0,他引:2
R J Loffeld E Stobberingh J P van Spreeuwel J A Flendrig J W Arends 《Journal of medical microbiology》1990,32(2):105-109
An enzyme linked immunosorbent assay (ELISA) with a sonicated suspension of Helicobacter (Campylobacter) pylori as antigen was used to detect anti-H. pylori antibodies in 517 patients without dyspepsia or peptic ulcer symptoms and 401 healthy blood donors. The criterion of seropositivity was determined from a receiver operating curve computed with the values of optical densities of 48 sera from dyspeptic patients with proven helicobacter-associated gastritis and 16 sera from dyspeptic patients with normal antral mucosa and no microbiological or histological evidence of H. pylori infection. The 227 (44%) seropositive persons amongst the patient group appeared to be significantly higher than the 142 (35%) sera with antibodies in the blood donors tested (p less than 0.03), even when adjustment was made for increasing age. We conclude that the prevalence of antibodies against H. pylori increases with age and that although antibodies are more prevalent in patients attending a hospital than in healthy blood donors, seropositivity suggestive of current or past infection can be found in one third of a randomly chosen population of blood donors. 相似文献