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71.
72.
Yi Ma Robin K. Walker Yichen Zhao Gerald A. Berkowitz 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(48):19852-19857
Little is known about molecular steps linking perception of pathogen invasion by cell surface sentry proteins acting as pattern recognition receptors (PRRs) to downstream cytosolic Ca2+ elevation, a critical step in plant immune signaling cascades. Some PRRs recognize molecules (such as flagellin) associated with microbial pathogens (pathogen-associated molecular patterns, PAMPs), whereas others bind endogenous plant compounds (damage-associated molecular patterns, DAMPs) such as peptides released from cells upon attack. This work focuses on the Arabidopsis DAMPs plant elicitor peptides (Peps) and their receptors, PEPR1 and PEPR2. Pep application causes in vivo cGMP generation and downstream signaling that is lost when the predicted PEPR receptor guanylyl cyclase (GC) active site is mutated. Pep-induced Ca2+ elevation is attributable to cGMP activation of a Ca2+ channel. Some differences were identified between Pep/PEPR signaling and the Ca2+-dependent immune signaling initiated by the flagellin peptide flg22 and its cognate receptor Flagellin-sensing 2 (FLS2). FLS2 signaling may have a greater requirement for intracellular Ca2+ stores and inositol phosphate signaling, whereas Pep/PEPR signaling requires extracellular Ca2+. Maximal FLS2 signaling requires a functional Pep/PEPR system. This dependence was evidenced as a requirement for functional PEPR receptors for maximal flg22-dependent Ca2+ elevation, H2O2 generation, defense gene [WRKY33 and Plant Defensin 1.2 (PDF1.2)] expression, and flg22/FLS2-dependent impairment of pathogen growth. In a corresponding fashion, FLS2 loss of function impaired Pep signaling. In addition, a role for PAMP and DAMP perception in bolstering effector-triggered immunity (ETI) is reported; loss of function of either FLS2 or PEPR receptors impaired the hypersensitive response (HR) to an avirulent pathogen. 相似文献
73.
Grant SF Glessner JT Bradfield JP Zhao J Tirone JE Berkowitz RI Hakonarson H Sondheimer N 《International journal of obesity (2005)》2012,36(1):80-83
Mitochondrial electron transport has a central role in regulating energy supply within a cell. We hypothesized that mitochondrial variants or increased levels of mitochondrial heteroplasmy could be associated with common childhood obesity through their effects on mitochondrial function. To investigate this question, we queried two genome-wide genotyped childhood obesity datasets, consisting of 1080 European-American (EA) obese children (defined as BMI ≥ 95th percentile) together with 2500 EA lean controls (defined as BMI<50th percentile) and 1479 African-American (AA) obese children and 1575 AA lean controls. Association was not observed between childhood obesity and any of the assayed mitochondrial polymorphisms in either ethnicity. We also found no observable differences in heteroplasmy between each obese and non-obese group. Finally, we analyzed the quantitative mitochondrial genotype cells generated, whether they exceeded the heteroplasmy threshold or not. With this more lenient test, we found six positions with a significant difference between EA cases and controls (P<1 × 10(-4)). However, when evaluating the AA data set, no differences were noted at these sites, suggesting that our initial observations were because of chance rather than a meaningful relationship to childhood obesity. As such, it is unlikely that common mitochondrial polymorphisms or heteroplasmy have a role in childhood obesity. 相似文献
74.
Bruce A. Berkowitz Robert H. Podolsky Karen Lins Childers Robin Roberts Michael Schneider Emma Graffice Kenan Sinan Ali Berri Lamis Harp 《Investigative ophthalmology & visual science》2021,62(6)
PurposeTo test the hypothesis that acutely correcting a sustained presence of outer retina free radicals measured in vivo in 24-month-old mice corrects their reduced visual performance.MethodsMale C57BL/6J mice two and 24 months old were noninvasively evaluated for unremitted production of paramagnetic free radicals based on whether 1/T1 in retinal laminae are reduced after acute antioxidant administration (QUEnch-assiSTed [QUEST] magnetic resonance imaging [MRI]). Superoxide production was measured in freshly excised retina (lucigenin assay). Combining acute antioxidant administration with optical coherence tomography (i.e., QUEST OCT) tested for excessive free radical–induced shrinkage of the subretinal space volume. Combining antioxidant administration with optokinetic tracking tested for a contribution of uncontrolled free radical production to cone-based visual performance declines.ResultsAt two months, antioxidants had no effect on 1/T1 in vivo in any retinal layer. At 24 months, antioxidants reduced 1/T1 only in superior outer retina. No age-related change in retinal superoxide production was measured ex vivo, suggesting that free radical species other than superoxide contributed to the positive QUEST MRI signal at 24 months. Also, subretinal space volume did not show evidence for age-related shrinkage and was unresponsive to antioxidants. Finally, visual performance declined with age and was not restored by antioxidants that were effective per QUEST MRI.ConclusionsAn ongoing uncontrolled production of outer retina free radicals as measured in vivo in 24 mo C57BL/6J mice appears to be insufficient to explain reductions in visual performance. 相似文献
75.
76.
I. Sukhotnik I. Aranovich Y. Ben Shahar N. Bitterman Y. Pollak D. Berkowitz D. Chepurov A. G. Coran A. Bitterman 《Pediatric surgery international》2016,32(2):161-168
Purpose
Taurine (TAU) is a sulfur-containing amino acid that is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation. Several studies have established that treatment with TAU significantly protects cerebral, cardiac and testicular injury from ischemia–reperfusion (IR). The purpose of the present study was to examine the effect of TAU on intestinal recovery and enterocyte turnover after intestinal IR injury in rats.Methods
Male Sprague–Dawley rats were divided into four experimental groups: (1) Sham rats that underwent laparotomy, (2) Sham-TAU rats that underwent laparotomy and were treated with intraperitoneal (IP) TAU (250 mg/kg); (3) IR-rats that underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 48 h of reperfusion, and (4) IR-TAU rats that underwent IR and were treated with IP TAU (250 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park’s injury score, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. The expression of Bax, Bcl-2, p-ERK and caspase-3 in the intestinal mucosa was determined using Western blot and immunohistochemistry.Results
Treatment with TAU resulted in a significant decrease in Park’s injury score compared to IR animals. IR-TAU rats also demonstrated a significant increase in mucosal weight in jejunum and ileum, villus height in jejunum and ileum and crypt depth in ileum compared to IR animals. IR-TAU rats also experienced significantly lower apoptotic indices in jejunum and ileum which was accompanied by a higher Bcl-2/Bax ratio compared to IR animals.Conclusions
Treatment with taurine prevents gut mucosal damage and inhibits intestinal epithelial cell apoptosis following intestinal IR in a rat.77.
Nurse practitioners as attending providers for injured workers: evaluating the effect of role expansion on disability and costs 总被引:1,自引:0,他引:1
BACKGROUND: A 3-year pilot program to expand the role of nurse practitioners (NPs) in the Washington State workers' compensation system was implemented on July 1, 2004. This legislation authorized NPs to independently perform most functions of an attending physician. OBJECTIVE: The purpose of this study was to assess the impact of this legislation by examining medical costs and disability outcomes for injured workers in the care of NPs benchmarked against those in the care of primary care physicians (PCPs). RESEARCH DESIGN: This observational study compared NPs and PCPs in the role of attending provider based on the medical costs and disability outcomes of injured workers in their care. Comparisons controlled for sociodemographics, geographic location, injury, employment, and provider characteristics. DATA SOURCE: The Washington State Department of Labor and Industries provided claim and medical billing data for 29,949 injured workers who had an accident report filed by an NP or PCP between July 1, 2004 and June 30, 2005. Data were collected through June 30, 2006. RESULTS: NPs were more likely than PCPs to be located in rural areas and counties with high unemployment. The distributions of injury type and severity/complexity indicators were similar across provider types. The likelihood of any time loss was lower for NP claims, but duration of lost work time and medical costs did not significantly differ by provider type. CONCLUSIONS: Attending provider type is not a significant predictor of disability or medical costs for injured workers in Washington State. 相似文献
78.
79.
Yamamori T White AR Mattagajasingh I Khanday FA Haile A Qi B Jeon BH Bugayenko A Kasuno K Berkowitz DE Irani K 《Journal of molecular and cellular cardiology》2005,39(6):101-995
The p66shc adaptor protein mediates age-associated oxidative stress. We examined the role of p66shc in endothelial nitric oxide synthase (eNOS) signaling. Overexpression of p66shc inhibited eNOS-dependent NO production. RNAi-mediated down-regulation of endogenous p66shc led to activation of the proto-oncogene ras, and Akt kinase, with a corresponding increase in phosphorylation of eNOS at S1177 (S1179 on bovine eNOS). In rat aortic rings, down-regulation of p66shc suppressed the vasoconstrictor response to phenyephrine that was abrogated by treatment with the NOS inhibitor l-NAME, and enhanced vasodilation induced by sub-maximal doses of acetylcholine. These findings highlight a pivotal role for p66shc in inhibiting endothelial NO production, and endothelium-dependent vasorelaxation, that may provide important mechanistic information about endothelial dysfunction seen with aging. 相似文献
80.
Madan M Berkowitz SD Christie DJ Jennings LK Smit AC Sigmon KN Glazer S Tcheng JE 《American heart journal》2001,141(2):226-233
BACKGROUND: The platelet function analyzer PFA-100 (Dade Behring, Miami, Fla) evaluates platelet function by determining the time to occlusion of an aperture in a membrane coated with collagen and adenosine diphosphate or epinephrine as whole blood flows under shear stress conditions. Platelet aggregation causes aperture occlusion, and results are reported as closure time (CT). Interindividual variability is observed in the level of platelet inhibition achieved with use of the current abciximab dosing regimen (0.25-mg/kg bolus + 10-microg/min infusion for 12 hours). The relationships between specific levels of platelet inhibition and clinical efficacy and safety have not been fully established. METHODS AND RESULTS: We prospectively studied platelet function in 27 patients receiving abciximab during percutaneous coronary intervention. This evaluation included determinations of platelet-rich plasma aggregometry, receptor occupancy studies (D3 assay), and CT measurements at baseline and 10 minutes, 4 hours, 12 hours, and 24 hours after the bolus. All patients received abciximab, aspirin, and heparin; patients undergoing coronary stent implantation received aspirin and ticlopidine after the procedure. CT results were reported within 10 minutes after initiation of testing. For 96% of patients, CT was 300 seconds (maximum CT) immediately after abciximab bolus and remained so throughout the infusion. At 24 hours we observed variable recovery from platelet inhibition and in 72% of patients CT returned to normal (< or =130 seconds). CONCLUSIONS: Findings with the PFA-100 were similar to results observed with platelet aggregometry and receptor occupancy measurements. Most patients treated with abciximab exhibit normalized platelet function at 24 hours despite moderate levels of receptor occupancy, suggesting dissociation between occupancy and function. 相似文献