全文获取类型
收费全文 | 1945篇 |
免费 | 155篇 |
国内免费 | 1篇 |
出版年
2021年 | 13篇 |
2020年 | 14篇 |
2019年 | 19篇 |
2018年 | 20篇 |
2017年 | 18篇 |
2016年 | 38篇 |
2015年 | 61篇 |
2014年 | 73篇 |
2013年 | 100篇 |
2012年 | 125篇 |
2011年 | 117篇 |
2010年 | 80篇 |
2009年 | 82篇 |
2008年 | 108篇 |
2007年 | 140篇 |
2006年 | 111篇 |
2005年 | 120篇 |
2004年 | 104篇 |
2003年 | 108篇 |
2002年 | 120篇 |
2001年 | 31篇 |
2000年 | 21篇 |
1999年 | 37篇 |
1998年 | 37篇 |
1997年 | 28篇 |
1996年 | 28篇 |
1995年 | 21篇 |
1994年 | 27篇 |
1993年 | 25篇 |
1992年 | 27篇 |
1991年 | 19篇 |
1990年 | 11篇 |
1989年 | 21篇 |
1988年 | 19篇 |
1987年 | 14篇 |
1986年 | 7篇 |
1985年 | 14篇 |
1984年 | 12篇 |
1983年 | 13篇 |
1982年 | 12篇 |
1981年 | 15篇 |
1980年 | 9篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1976年 | 5篇 |
1974年 | 6篇 |
1971年 | 4篇 |
1968年 | 4篇 |
1965年 | 4篇 |
排序方式: 共有2101条查询结果,搜索用时 15 毫秒
71.
Rheal A. Towner Nataliya Smith Debra Saunders Patricia Coutinho De Souza Leah Henry Florea Lupu Robert Silasi-Mansat Marilyn Ehrenshaft Ronald P. Mason Sandra E. Gomez-Mejiba Dario C. Ramirez 《生物化学与生物物理学报:疾病的分子基础》2013,1832(12):2153-2161
Free radicals play a major role in gliomas. By combining immuno-spin-trapping (IST) and molecular magnetic resonance imaging (mMRI), in vivo levels of free radicals were detected within mice bearing orthotopic GL261 gliomas. The nitrone spin trap DMPO (5,5-dimethyl pyrroline N-oxide) was administered prior to injection of an anti-DMPO probe (anti-DMPO antibody covalently bound to a bovine serum albumin (BSA)–Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)–biotin MRI contrast agent) to trap tumor-associated free radicals. mMRI detected the presence of anti-DMPO adducts by either a significant sustained increase (p < 0.001) in MR signal intensity or a significant decrease (p < 0.001) in T1 relaxation, measured as %T1 change. In vitro assessment of the anti-DMPO probe indicated a significant decrease (p < 0.0001) in T1 relaxation in GL261 cells that were oxidatively stressed with hydrogen peroxide, compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised brain tissues. As a negative control a non-specific IgG antibody covalently bound to the albumin–Gd-DTPA–biotin construct was used. DMPO adducts were also confirmed in tumor tissue from animals administered DMPO, compared to non-tumor brain tissue. GL261 gliomas were found to have significantly increased malondialdehyde (MDA) protein adducts (p < 0.001) and 3-nitrotyrosine (3-NT) (p < 0.05) compared to normal mouse brain tissue, indicating increased oxidized lipids and proteins, respectively. Co-localization of the anti-DMPO probe with either 3-NT or 4-hydroxynonenal was also observed. This is the first report regarding the detection of in vivo levels of free radicals from a glioma model. 相似文献
72.
Bojun?Chen Debra?Bohnert Richard?Ben?BorgensEmail author Youngnam?ChoEmail author 《Journal of biological engineering》2013,7(1):15
Background
We continue our exploration of the large polysaccharide polymer Chitosan as an acute therapy for severe damage to the nervous system. We tested the action of subcutaneously injected nanoparticles (~ 100 – 200 nanometers in diameter; 1 mg per ml) against control injections (silica particle of the same size and concentration) in a standardized in vivo spinal cord injury model. These functional tests used standardized physiological measurements of evoked potentials arriving at the sensorimotor cortex subsequent to stimulation of the tibial nerve of the contralateral hindlimb. We further explored the degree of acetylation and molecular weight of chitosan on the success of sealing cell damage using specific probes of membrane integrity.Results
Not one of the control group showed restored conduction of evoked potentials stimulated from the tibial nerve of the hindleg – through the lesion – and recorded at the sensorimotor cortex of the brain. Investigation if the degree of acetylation and molecular weight impacted “membrane sealing” properties of Chitosan were unsuccessful. Dye - exchange membrane probes failed to show a difference between the comparators in the function of Chitosan in ex vivo injured spinal cord tests.Conclusions
We found that Chitosan nanoparticles effectively restore nerve impulse transmission through the crushed adult guinea pig spinal cord in vivo after severe crush/compression injury. The tests of the molecular weight (MW) and degree of acetylation did not produce any improvement in Chitosan’s membrane sealing properties.73.
Introduction
Skin and soft tissue infections (SSTIs) are common infections occurring in ambulatory and inpatient settings. The extent of complications associated with these infections by diabetes status is not well established.Methods
Using a very large repository database, we examined medical and pharmacy claims of individuals aged 0–64 between 2005 and 2010 enrolled in U.S. health plans. Diabetes, SSTIs, and SSTI-associated complications were identified by ICD-9 codes. SSTIs were stratified by clinical category and setting of initial diagnosis.Results
We identified 2,227,401 SSTI episodes, 10% of which occurred in diabetic individuals. Most SSTIs were initially diagnosed in ambulatory settings independent from diabetes status. Abscess/cellulitis was the more common SSTI group in diabetic and non-diabetic individuals (66% and 59%, respectively). There were differences in the frequencies of SSTI categories between diabetic and non-diabetic individuals (p<0.01). Among SSTIs diagnosed in ambulatory settings, the SSTI-associated complication rate was over five times higher in people with diabetes than in people without diabetes (4.9% vs. 0.8%, p<0.01) and SSTI-associated hospitalizations were 4.9% and 1.1% in patients with and without diabetes, respectively. Among SSTIs diagnosed in the inpatient setting, bacteremia/endocarditis/septicemia/sepsis was the most common associated complication occurring in 25% and 16% of SSTIs in patients with and without diabetes, respectively (p<0.01).Conclusions
Among persons with SSTIs, we found SSTI-associated complications were five times higher and SSTI-associated hospitalizations were four times higher, in patients with diabetes compared to those without diabetes. SSTI prevention efforts in individuals with diabetes may have significant impact on morbidity and healthcare resource utilization. 相似文献74.
Richard A. Humber Luiz F.N. Rocha Peter W. Inglis André Kipnis Christian Luz 《Fungal biology》2013,117(1):1-12
The entomopathogenic anamorphic genus Evlachovaea was described to differ from other fungi in forming its conidia obliquely to the axis of the conidiogenous cell and with successive conidia having alternate orientations with a zipper- or chevron-like arrangement resulting in flat, ribbon-like chains. Morphological and molecular studies of six Evlachovaea-like isolates baited from Central Brazilian soils using Triatoma infestans (a vector of Chagas disease) and of other entomopathogens with Evlachovaea-like conidiogenesis led to a re-evaluation of the status of this little known fungal genus. The Brazilian isolates formed two distinct groups based on gene sequences for both the internal transcribed spacer (ITS) and translation elongation factor (EF-1α) genes, morphology, and growth patterns; both groups also differed from the type species, Evlachovaea kintrischica. More detailed studies of these fungi indicated that the alternatingly oblique orientations of forming conidia are neither a stable nor invariant character (even on single phialides). Furthermore, the molecular cladistic analysis unambiguously placed the Evlachovaea isolates firmly within the genus Isaria (Hypocreales: Cordycipitaceae). The ITS sequences of E. kintrischica were very similar or even identical to those of Isaria amoenerosea and Isaria cateniobliqua, thereby suggesting that E. kintrischica is a synonym of one of these species, and that the genus Evlachovaea must be treated as a later synonym of Isaria, which must now be recognized to include several highly divergent modes of conidiogenesis. These taxonomic findings are discussed in the context of dramatic changes recently imposed on the nomenclatural standards used to determine the correct names of all pleomorphic fungi. 相似文献
75.
Joseph E. Donnelly Jeffery J. Honas Bryan K. Smith Matthew S. Mayo Cheryl A. Gibson Debra K. Sullivan Jaehoon Lee Stephen D. Herrmann Kate Lambourne Rik A. Washburn 《Obesity (Silver Spring, Md.)》2013,21(3):E219-E228
Exercise is recommended by public health agencies for weight management; however, the role of exercise is generally considered secondary to energy restriction. Few studies exist that have verified completion of exercise, measured the energy expenditure of exercise, and prescribed exercise with equivalent energy expenditure across individuals and genders.
Objective:
The objective of this study was to evaluate aerobic exercise, without energy restriction, on weight loss in sedentary overweight and obese men and women.Design and Methods:
This investigation was a randomized, controlled, efficacy trial in 141 overweight and obese participants (body mass index, 31.0 ± 4.6 kg/m2; age 22.6 ± 3.9 years). Participants were randomized (2:2:1 ratio) to exercise at either 400 kcal/session or 600 kcal/session or to a nonexercise control. Exercise was supervised, 5 days/week, for 10 months. All participants were instructed to maintain usual ad libitum diets. Because of the efficacy design, completion of ≥90% of exercise sessions was an a priori definition of per protocol, and these participants were included in the analysis.Results:
Weight loss from baseline to 10 months for the 400 and 600 kcal/session groups was 3.9 ± 4.9 kg (4.3%) and 5.2 ± 5.6 kg (5.7%), respectively, compared with weight gain for controls of 0.5 ± 3.5 kg (0.5%) (P < 0.05). Differences for weight loss from baseline to 10 months between the exercise groups and differences between men and women within groups were not statistically significant.Conclusions:
Supervised exercise, with equivalent energy expenditure, results in clinically significant weight loss with no significant difference between men and women. 相似文献76.
Viswanathan Rajagopalan Youhua Zhang Kaie Ojamaa Yue-feng Chen Alessandro Pingitore Christine J. Pol Debra Saunders Krithika Balasubramanian Rheal A. Towner A. Martin Gerdes 《PloS one》2016,11(3)
Background
A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI.Methods and Results
Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy.Conclusions
Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans. 相似文献77.
Lucy A. Howey Emily R. Tolentino Yannis P. Papastamatiou Edward J. Brooks Debra L. Abercrombie Yuuki Y. Watanabe Sean Williams Annabelle Brooks Demian D. Chapman Lance K.B. Jordan 《Ecology and evolution》2016,6(15):5290-5304
Comprehension of ecological processes in marine animals requires information regarding dynamic vertical habitat use. While many pelagic predators primarily associate with epipelagic waters, some species routinely dive beyond the deep scattering layer. Actuation for exploiting these aphotic habitats remains largely unknown. Recent telemetry data from oceanic whitetip sharks (Carcharhinus longimanus) in the Atlantic show a strong association with warm waters (>20°C) less than 200 m. Yet, individuals regularly exhibit excursions into the meso‐ and bathypelagic zone. In order to examine deep‐diving behavior in oceanic whitetip sharks, we physically recovered 16 pop‐up satellite archival tags and analyzed the high‐resolution depth and temperature data. Diving behavior was evaluated in the context of plausible functional behavior hypotheses including interactive behaviors, energy conservation, thermoregulation, navigation, and foraging. Mesopelagic excursions (n = 610) occurred throughout the entire migratory circuit in all individuals, with no indication of site specificity. Six depth‐versus‐time descent and ascent profiles were identified. Descent profile shapes showed little association with examined environmental variables. Contrastingly, ascent profile shapes were related to environmental factors and appear to represent unique behavioral responses to abiotic conditions present at the dive apex. However, environmental conditions may not be the sole factors influencing ascents, as ascent mode may be linked to intentional behaviors. While dive functionality remains unconfirmed, our study suggests that mesopelagic excursions relate to active foraging behavior or navigation. Dive timing, prey constituents, and dive shape support foraging as the most viable hypothesis for mesopelagic excursions, indicating that the oceanic whitetip shark may regularly survey extreme environments (deep depths, low temperatures) as a foraging strategy. At the apex of these deep‐water excursions, sharks exhibit a variable behavioral response, perhaps, indicating the presence or absence of prey. 相似文献
78.
Debra L. Hanson Ruiguang Song Silvina Masciotra Angela Hernandez Trudy L. Dobbs Bharat S. Parekh S. Michele Owen Timothy A. Green 《PloS one》2016,11(4)
HIV incidence estimates are used to monitor HIV-1 infection in the United States. Use of laboratory biomarkers that distinguish recent from longstanding infection to quantify HIV incidence rely on having accurate knowledge of the average time that individuals spend in a transient state of recent infection between seroconversion and reaching a specified biomarker cutoff value. This paper describes five estimation procedures from two general statistical approaches, a survival time approach and an approach that fits binomial models of the probability of being classified as recently infected, as a function of time since seroconversion. We compare these procedures for estimating the mean duration of recent infection (MDRI) for two biomarkers used by the U.S. National HIV Surveillance System for determination of HIV incidence, the Aware BED EIA HIV-1 incidence test (BED) and the avidity-based, modified Bio-Rad HIV-1/HIV-2 plus O ELISA (BRAI) assay. Collectively, 953 specimens from 220 HIV-1 subtype B seroconverters, taken from 5 cohorts, were tested with a biomarker assay. Estimates of MDRI using the non-parametric survival approach were 198.4 days (SD 13.0) for BED and 239.6 days (SD 13.9) for BRAI using cutoff values of 0.8 normalized optical density and 30%, respectively. The probability of remaining in the recent state as a function of time since seroconversion, based upon this revised statistical approach, can be applied in the calculation of annual incidence in the United States. 相似文献
79.
80.
Michael J Stobart Debra Parchaliuk Sharon LR Simon Jillian LeMaistre Jozef Lazar Richard Rubenstein J David Knox 《Molecular neurodegeneration》2007,2(1):1-13