收费全文 | 52437篇 |
免费 | 3780篇 |
国内免费 | 257篇 |
耳鼻咽喉 | 517篇 |
儿科学 | 1915篇 |
妇产科学 | 1365篇 |
基础医学 | 7991篇 |
口腔科学 | 789篇 |
临床医学 | 5050篇 |
内科学 | 11675篇 |
皮肤病学 | 1173篇 |
神经病学 | 5876篇 |
特种医学 | 1116篇 |
外科学 | 4338篇 |
综合类 | 294篇 |
现状与发展 | 1篇 |
一般理论 | 43篇 |
预防医学 | 4775篇 |
眼科学 | 858篇 |
药学 | 4026篇 |
中国医学 | 136篇 |
肿瘤学 | 4536篇 |
2024年 | 67篇 |
2023年 | 618篇 |
2022年 | 461篇 |
2021年 | 2420篇 |
2020年 | 1398篇 |
2019年 | 1792篇 |
2018年 | 1969篇 |
2017年 | 1593篇 |
2016年 | 1753篇 |
2015年 | 1902篇 |
2014年 | 2472篇 |
2013年 | 3103篇 |
2012年 | 4563篇 |
2011年 | 4565篇 |
2010年 | 2422篇 |
2009年 | 2067篇 |
2008年 | 3450篇 |
2007年 | 3440篇 |
2006年 | 3108篇 |
2005年 | 2826篇 |
2004年 | 2622篇 |
2003年 | 2337篇 |
2002年 | 2106篇 |
2001年 | 246篇 |
2000年 | 187篇 |
1999年 | 255篇 |
1998年 | 335篇 |
1997年 | 285篇 |
1996年 | 195篇 |
1995年 | 184篇 |
1994年 | 181篇 |
1993年 | 140篇 |
1992年 | 98篇 |
1991年 | 83篇 |
1990年 | 65篇 |
1989年 | 76篇 |
1988年 | 73篇 |
1987年 | 64篇 |
1986年 | 60篇 |
1985年 | 60篇 |
1984年 | 83篇 |
1983年 | 66篇 |
1982年 | 77篇 |
1981年 | 64篇 |
1980年 | 60篇 |
1979年 | 29篇 |
1978年 | 31篇 |
1977年 | 34篇 |
1976年 | 25篇 |
1974年 | 19篇 |
Purpose
The pharmacokinetic (PK) parameters of many drugs are altered as a consequence of the pathophysiological changes associated with critical illness. The critically ill population presents challenges when titrating infusions of sedatives and analgesics to maintain optimal sedation and pain levels. This systematic review examined the PK data in critically ill adult patients with prolonged infusions (>24 hours) of commonly used sedatives and analgesics to highlight possible altered PK parameters compared with noncritically ill patients.Methods
A literature search of PK studies was performed by using MEDLINE (1946–December 2017) and EMBASE (1910–December 2017); we identified further studies by citation tracking (Web of Science) and checked references of retrieved studies and review articles. All studies were included that were published in English, Chinese, or German; conducted in critically ill adult patients receiving lorazepam, midazolam, propofol, dexmedetomidine, sufentanil, alfentanil, remifentanil, morphine, or fentanyl infusion for ≥24 hours; and reported PK parameters. When appropriate, we conducted a meta-analysis on volume of distribution at steady state (Vdss) (liters), clearance (Cl) (liters per hour), and elimination t1/2 (hours) by using a DerSimonian-Laird random effects model to estimate the summary mean and 95% CIs. Results were compared with commonly reported PK ranges in 70-kg noncritically ill patients.Findings
Thirty-three randomized controlled trials and prospective cohort studies were identified involving 1803 adult critically ill patients with 35 drug treatment arms: fifteen midazolam (n?=?906) studies, three dexmedetomidine (n?=?561), nine propofol (n?=?165), four lorazepam (n?=?86), one morphine (n?=?20), two remifentanil (n?=?55), and one sufentanil (n?=?10). Each study showed large variations in Vdss, Cl, and elimination t1/2 within and between individual participants. High clinical and methodical heterogeneity between the dexmedetomidine studies prevented the direct comparison of PK parameters between critically ill and noncritically ill patients. Use of midazolam, propofol, and lorazepam in critically ill patients was associated with at least a 2- to 4-fold increase in Vdss compared with noncritically ill patients; Cl decreased ~2-fold for midazolam and 10-fold for morphine. Critically ill patients receiving prolonged infusions of midazolam, propofol, remifentanil, and sufentanil had at least 2-fold longer elimination or terminal t1/2 than noncritically ill patients.Implications
These findings show a marked difference in many PK parameters from those reported for noncritically ill patients. Initiatives to improve the delivery of prolonged sedatives and analgesic infusions should be informed by PK parameters (Vdss, context-sensitive t1/2, and elimination t1/2) and data derived from critically ill patients. 相似文献Background
Various endocrine signals oscillate over the 24‐hour period and so does the responsiveness of target tissues. These daily oscillations do not occur solely in response to external stimuli but are also under the control of an intrinsic circadian clock.Design
We searched the PubMed database to identify studies describing the associations of clock genes with endocrine diseases.Results
Various human single nucleotide polymorphisms of brain and muscle ARNT‐like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK) genes exhibited significant associations with type 2 diabetes mellitus. ARNTL2 gene expression and upregulation of BMAL1 and PER1 were associated with the development of type 1 diabetes mellitus. Thyroid hormones modulated PER2 expression in a tissue‐specific way, whereas BMAL1 regulated the expression of type 2 iodothyronine deiodinase in specific tissues. Adrenal gland and adrenal adenoma expressed PER1, PER2, CRY2, CLOCK and BMAL1 genes. Adrenal sensitivity to adrenocorticotrophin was also affected by circadian oscillations. A significant correlation between the expression of propio‐melanocorticotrophin and PER 2, as well as between prolactin and CLOCK, was found in corticotroph and lactosomatotroph cells, respectively, in the pituitary. Clock genes and especially BMAL1 showed an important role in fertility, whereas oestradiol and androgens exhibited tissue‐specific effects on clock gene expression. Metabolic disorders were also associated with circadian dysregulation according to studies in shift workers.Conclusions
Clock genes are associated with various endocrine disorders through complex mechanisms. However, data on humans are scarce. Moreover, clock genes exhibit a tissue‐specific expression representing an additional level of regulation. Their specific role in endocrine disorders and their potential implications remain to be further clarified. 相似文献Purpose
The accumulation of advanced glycation end products (AGEs) in local tissue is an important cause of low-grade inflammation and oxidative stress and is linked to late diabetic complications. Physical activity has various beneficial cardiometabolic effects in type 1 diabetes (T1D) and is associated with lower frequency of chronic complications of diabetes, although the specific mechanisms still remain unclear. The present study determines the association between self-reported physical activity and skin autofluorescence (AF), a marker of tissue accumulation of AGEs in adults with T1D.Methods
We enrolled 119 patients (63 women), aged 34 years (interquartile range [IQR], 26–41 years), with T1D duration of 17 years (IQR, 12–25 years), glycosylated hemoglobin (HbA1c) of 7.9% (IQR, 7.1%–8.9%) referred to an outpatient diabetes clinic. Patients with diabetes duration of <5 years, age >65 years, concomitant diabetic ketoacidosis, and severe complications that restrict physical activity (eg, diabetic foot, diabetic proliferative retinopathy, blindness) were excluded. Physical activity was measured with the short version of the International Physical Activity Questionnaire (IPAQ-SF), and raw scores were then log-transformed because of non-normality. The accumulation of AGEs in the skin was assessed on the basis of skin AF. Correlations between AF and various laboratory and clinical findings were assessed, and multivariate linear regression analysis was used to examine factors that influenced AGEs.Findings
Skin AF correlated positively with age (Spearman’s coefficient [Rs] = 0.47; P < 0.0001), HbA1c (Rs = 0.30; P = 0.001), waist-to-hip ratio (WHR; Rs = 0.23; P = 0.02), and negatively with logIPAQ-SF (Rs = –0.28; P = 0.002). A stepwise multivariable linear regression analysis indicated age (β = 0.46; P < 0.0001), HbA1c (β = 0.21; P = 0.01), and logIPAQ-SF score (β = –0.17; P = 0.04) as predictors of the skin AF after adjustment for sex and WHR (R2 = 0.36; P < 0.0001).Implications
Higher physical activity is related to lower accumulation of AGEs in patients with T1D. Our study provides new insight into the beneficial effects of physical activity in T1D according to tissue accumulation of AGEs. 相似文献Introduction
The purpose of this review is to present the current and emerging treatment alternatives for Leber’s hereditary optic neuropathy (LHON), emphasizing the most recent use of idebenone and stem cells or gene therapy.Methods
A comprehensive literature review was performed at the PubMed database regarding the various treatment modalities for LHON.Results
Treatment modalities for LHON include nutritional supplements, activators of mitochondrial biogenesis, brimonidine, and symptomatic and supportive treatment, but nowadays attention is being paid to idebenone and gene therapy or stem cells.Conclusion
The treatment of LHON remains challenging, given the nature of the disease and its prognosis.The aim of this study was to evaluate the utility of added DWI sequences as an adjunct to traditional MR imaging in the evaluation of abnormal placentation in patients with suspicion for placenta accreta spectrum abnormality or morbidly adherent placenta (MAP).
Materials and methodsThe study was approved by local ethics committee. The subjects included pregnant women with prenatal MRI performed between July 2013 to July 2015. All imaging was performed on a Philips 1.5T MR scanner using pelvic phased-array coil. Only T2-weighted and diffusion-weighted imaging (DWI) series were compiled for review. Two randomized imaging sets were created: set 1 included T2-weighted series only (T2W); set 2 included T2W with DWI series together (T2W + DWI). Three radiologists, blinded to history and pathology, reviewed the imaging, with 2 weeks of time between the two image sets. Sensitivity, specificity, and overall accuracy for MAP were calculated and compared between T2W only and T2W + DWI reads. Associations between imaging findings and invasion on pathology were tested using the Chi-squared test. Confidence scores, inter-reader agreement, and systematic differences were documented.
ResultsA total of 17 pregnant women were included in the study. 8 cases were pathologically diagnosed with MAP. There were no significant differences in the diagnostic accuracy between T2W and T2W + DWI in the diagnosis of MAP in terms of overall accuracy (62.7% for T2W vs. 68.6% for T2W + DWI, p = 0.68), sensitivity (70.8% for T2W vs. 95.8% for T2W + DWI, p = 0.12), and specificity (55.6% for T2W vs. 44.4% for T2W + DWI, p = 0.49). There was no significant difference in the diagnostic confidence between the review of T2W images alone and the T2W + DWI review (mean 7.3 ± 1.8 for T2W vs. 7.5 ± 1.8 for T2W + DWI, p = 0.37).
ConclusionWith the current imaging technique, addition of DWI sequence to the traditional T2W images cannot be shown to significantly increase the accuracy or reader confidence for diagnosis of placenta accreta spectrum abnormality. However, DWI does improve identification of abnormalities in the placental–myometrial interface.
相似文献