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991.
PURPOSE: This report describes the clinical and in vivo microstructural features of the cornea in a case of Maroteaux-Lamy syndrome. METHODS: A 17-year-old female with Maroteaux-Lamy syndrome was examined by slit-lamp biomicroscopy, Orbscan II slit-scanning elevation topography, and in vivo confocal microscopy. RESULTS: Slit-lamp biomicroscopy revealed bilateral, altered corneal transparency involving the posterior half of the stroma. Funduscopy revealed bilateral small, crowded optic discs, and radial macula retinal folds.On in vivo confocal microscopy, the middle and posterior stroma were clearly visualized and exhibited well-defined, unusually shaped keratocytes. These cells contained single or multiple hyporeflective regions with well-defined borders that ranged from 1 to 11.6 microm in diameter. These abnormal keratocytes were particularly abundant in the posterior stroma and sparse in the anterior stroma. CONCLUSIONS: This is the first case of Maroteaux-Lamy syndrome in which altered corneal transparency has been imaged by in vivo confocal microscopy and macula retinal folds have been described. 相似文献
992.
STUDY OBJECTIVE: To compare the efficacy and safety of plant sterols and stanols as well as policosanol in the treatment of coronary heart disease, as measured by a reduction in low-density lipoprotein cholesterol (LDL) levels. DESIGN: Systematic review and meta-analysis of randomized controlled trials. PATIENTS: A total of 4596 patients from 52 eligible studies. MEASUREMENTS AND MAIN RESULTS: We searched MEDLINE, EMBASE, the Web of Science, and the Cochrane Library from January 1967-June 2003 to identify pertinent studies. Reduction of LDL levels was the primary end point; effects on other lipid parameters and withdrawal of study patients due to adverse effects were the secondary end points. Weighted estimates of percent change in LDL were -11.0% for plant sterol and stanol esters 3.4 g/day (range 2-9 g/day [893 patients]) versus -2.3% for placebo (769 patients) in 23 eligible studies, compared with -23.7% for policosanol 12 mg/day (range 5-40 mg/day [1528 patients]) versus -0.11% for placebo (1406 patients) in 29 eligible studies. Cumulative p values were significantly different from placebo for both (p<0.0001). The net LDL reduction in the treatment groups minus that in the placebo groups was greater with policosanol than plant sterols and stanols (-24% versus -10%, p<0.0001). Policosanol also affected total cholesterol, high-density lipoprotein cholesterol (HDL), and triglyceride levels more favorably than plant sterols and stanols. Policosanol caused a clinically significant decrease in the LDL:HDL ratio. Pooled withdrawal rate due to adverse effects and combined relative risk for patients who withdrew were 0% and 0.84, respectively (95% confidence interval [CI] 0.36-1.95, p=0.69), for plant sterols and stanols across 20 studies versus 0.86% and 0.31, respectively (95% CI 0.20-0.48, p<0.0001), for policosanol across 28 studies. CONCLUSION: Plant sterols and stanols and policosanol are well tolerated and safe; however, policosanol is more effective than plant sterols and stanols for LDL level reduction and more favorably alters the lipid profile, approaching antilipemic drug efficacy. 相似文献
993.
994.
Liu H Liu J van Breemen RB Thatcher GR Bolton JL 《Chemical research in toxicology》2005,18(2):162-173
Although selective estrogen receptor modulators (SERMs) are useful in the treatment and prevention of breast cancer, the SERM tamoxifen has been associated with an increased risk of endometrial cancer possibly due to metabolism to electrophilic quinoids. Another SERM, arzoxifene is currently in clinical trials for the treatment of breast cancer, and since it has similar structural characteristics to tamoxifen, it also has the potential to form quinoids. In the current study, the active form of arzoxifene in vivo, desmethylated arzoxifene (DMA), was synthesized and chemically or enzymatically oxidized to DMA diquinone methide. The half-life of DMA diquinone methide at physiological pH and temperature was approximately 15 s. Reaction of DMA diquinone methide with glutathione (GSH) gave four mono-GSH conjugates, two di-GSH conjugates, and one tri-GSH conjugate. In incubations of DMA with GSH and either rat or human liver microsomes, DMA o-quinone-GSH conjugates were detected in addition to DMA diquinone methide-GSH conjugates. A DMA diquinone methide-deoxyguanosine adduct was detected following the incubation of DMA diquinone methide with deoxynucleosides. In preliminary studies with a human breast cancer cell line, DMA induced dose-dependent DNA damage and was more effective at causing DNA damage than raloxifene. These results suggest that DMA can be metabolized to electrophilic/redox-active quinoids, which have the potential to cause toxicity in vivo. A new fluorinated derivative unable to form a diquinone methide, 4'-F-DMA, was synthesized. 4'-F-DMA showed similar estrogen receptor (ER) binding affinity as compared to DMA. The antiestrogenic activity as measured by inhibition of estradiol-mediated induction of alkaline phosphatase activity in Ishikawa cells showed 10-fold lower activity for 4'-F-DMA compared to DMA; however, the antiestrogenic activity was comparable to raloxifene. In microsomal incubations of 4'-F-DMA in the presence of GSH, no GSH adducts were detected. These data suggest that 4'-F-DMA might be a promising SERM with similar activity to DMA and raloxifene and less toxicity. 相似文献
995.
Phosgene (COCl(2)) exposure affects an influx of inflammatory cells into the lung, which can be reduced in an animal model by pretreatment with colchicine. Inflammation in the respiratory tract can be associated with an increase in airway hyperreactivity. We tested the hypotheses that (1) phosgene exposure increases airway reactivity and (2) colchicine can decrease this elevation. Sprague Dawley rats (70 d old; male) were exposed to 1 ppm COCl(2) for 1 h. Airway reactivity was tested at 0, 4, and 24 h postexposure by infusing anesthetized animals intravenously with acetylcholine and assessing expiratory resistance and dynamic compliance. Immediately and 4 h postexposure, a significant change in expiratory resistance and dynamic compliance was observed in those animals exposed to COCl(2), while at 24 h this response was greater. A second experiment was performed in rats pretreated with colchicine (1 mg/kg) or saline given intraperitoneally, exposed to 1 ppm COCl(2) for 1 h, with both expiratory resistance and dynamic compliance assessed at 24 h. After exposure, cell differentials and protein in lavage were also quantitated. The results indicate that colchicine decreased neutrophil influx, protein accumulation, and changes in both expiratory resistance and dynamic compliance after COCl(2) exposure. Colchicine may affect injury and changes in expiratory resistance and dynamic compliance by diminishing the incursion of inflammatory cells, but other properties of this medication may also be responsible for the observed results. 相似文献
996.
997.
Mammalian transmembrane adenylyl cyclases synthesize a restricted plasmalemmal cAMP pool that is intensely endothelial barrier protective. Bacteria have devised mechanisms of transferring eukaryotic factor-dependent adenylyl cyclases into mammalian cells. Pseudomonas aeruginosa ExoY is one such enzyme that catalyzes cytosolic cAMP synthesis, with unknown function. Pseudomonas aeruginosa genetically modified to introduce only the ExoY toxin elevated cAMP 800-fold in pulmonary microvascular endothelial cells over 4 hours, whereas a catalytically deficient (ExoY(K81M)) strain did not increase cAMP. ExoY-derived cAMP was localized to a cytosolic microdomain not regulated by phosphodiesterase activity. In contrast to the barrier-enhancing actions of plasmalemmal cAMP, the ExoY cytosolic cAMP pool induced endothelial gap formation and increased the filtration coefficient in the isolated perfused lung. These findings collectively illustrate a previously unrecognized mechanism of hyperpermeability induced by rises in cytosolic cAMP. 相似文献
998.
de Chadarévian JP Guzman MA Pascasio JM Arthur LG 《Pediatric and developmental pathology》2012,15(2):96-100
We report the clinical-pathologic study of 8 cases of pediatric benign, postobstructive, appendiceal mucus retention in patients 3-15 years of age. The appendices showed very limited acute inflammation. Their most significant change consisted of minimal to mild dilatation of the distal lumen, which was filled with mucus and lined by an epithelium showing often dramatic increase in mucus cells devoid of atypia and without any of the villous proliferation reported in instances of "mucosal hyperplasia" observed in adult patients. In all 8 cases, there was seepage of mucus through the appendiceal wall into the surrounding tissue, eliciting a macrophagic reaction. Proximal to the zones of mucus retention, the lumen of 2 of the appendices was obstructed by a fecalith, and 2 exhibited fibrous obliteration of the lumen at that site. We believe the condition results from obstruction and focal inflammation, which isolate the distal portion of the appendix and elicit goblet cell metaplasia, the secretion of which is followed by luminal distention, eventual rupture, and seepage of mucus within the wall and the mesoappendix. The clinical and radiologic picture of this condition may be mistaken for that of an acute appendicitis complicated by rupture and abscess formation. The report provides an opportunity to describe and characterize "appendiceal mucosal goblet cell metaplasia," a seldom mentioned entity associated with benign appendiceal obstructive mucus retention in children. 相似文献
999.
Martha G Welch Myron A Hofer Susan A Brunelli Raymond I Stark Howard F Andrews Judy Austin Michael M Myers 《BMC pediatrics》2012,12(1):1-17
Background
The stress that results from preterm birth, requisite acute care and prolonged physical separation in the Neonatal Intensive Care Unit (NICU) can have adverse physiological/psychological effects on both the infant and the mother. In particular, the experience compromises the establishment and maintenance of optimal mother-infant relationship, the subsequent development of the infant, and the mother's emotional well-being. These findings highlight the importance of investigating early interventions that are designed to overcome or reduce the effects of these environmental insults and challenges.Methods
This study is a randomized controlled trial (RCT) with blinded assessment comparing Standard Care (SC) with a novel Family Nurture Intervention (FNI). FNI targets preterm infants born 26-34 weeks postmenstrual age (PMA) and their mothers in the NICU. The intervention incorporates elements of mother-infant interventions with known efficacy and organizes them under a new theoretical context referred to collectively as calming activities. This intervention is facilitated by specially trained Nurture Specialists in three ways: 1) In the isolette through calming interactions between mother and infant via odor exchange, firm sustained touch and vocal soothing, and eye contact; 2) Outside the isolette during holding and feeding via the Calming Cycle; and 3) through family sessions designed to engage help and support the mother. In concert with infant neurobehavioral and physiological assessments from birth through 24 months corrected age (CA), maternal assessments are made using standard tools including anxiety, depression, attachment, support systems, temperament as well as physiological stress parameters. Quality of mother-infant interaction is also assessed. Our projected enrolment is 260 families (130 per group).Discussion
The FNI is designed to increase biologically important activities and behaviors that enhance maternally-mediated sensory experiences of preterm infants, as well as infant-mediated sensory experiences of the mother. Consequently, we are enlarging the testing of preterm infant neurodevelopment beyond that of previous research to include outcomes related to mother-infant interactions and mother-infant co-regulation. Our primary objective is to determine whether repeated engagement of the mother and her infant in the intervention's calming activities will improve the infant's developmental trajectory with respect to multiple outcomes. Our secondary objective is to assess the effectiveness of FNI in the physiological and psychological co-regulation of the mother and infant. We include aspects of neurodevelopment that have not been comprehensively measured in previous NICU interventions.Trial Registration
ClinicalTrials.gov: NCT01439269 相似文献1000.