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31.

Background

There is increasing policy emphasis on adverse childhood experiences (ACEs). We aimed to assess the relative contributions of these experiences and socioeconomic factors to educational attainment and health.

Methods

Using data collected between 1991 and 2014, from a UK cohort (ALSPAC), we assessed associations of having had ACEs between birth and 16 years of age (sexual, physical, emotional abuse; emotional neglect; parental substance abuse, mental illness, criminal conviction, or separation; violence between parents; and bullying) with obtaining five or more good GCSEs (grades A* to C, n=9959, assessed through linkage to the National Pupil Database) and health at age 17 (depression, obesity, harmful alcohol use, smoking, and illicit drug use, n=4917, assessed through research clinic measurements and self-completed computer questionnaires). ACEs were assessed using both prospective (reports by main caregiver at time of ACE occurrence or very soon afterwards) and retrospective (reports by 23 year old adults looking back at their childhood) questionnaires and an ACE score was calculated by summing the number of ACE an individual experienced. We adjusted for a wide range of socioeconomic and family factors. We calculated population attributable fractions (PAF) for each outcome for four or more ACEs and key socioeconomic and demographic indicators.

Findings

Most participants (84%) experienced at least one adverse experience (24% ≥4). ACE score was associated with lower educational attainment and worse adolescent health. The association with educational attainment reduced by about half after adjustment for socioeconomic and family factors; associations with adolescent health also attenuated, but to a lesser degree. We assessed PAF for each outcome according to experiencing four or more ACEs (24%), low maternal education (30%), manual social class (24%), and maternal smoking during pregnancy (27%). For depression and illicit drug use, PAFs were highest for four or more ACEs (14% and 15%, respectively). For these outcomes, the PAF for maternal smoking during pregnancy was also high (both 10%). For all other outcomes, PAFs were higher for socioeconomic factors or maternal smoking than for ACEs.

Interpretation

A key limitation of our study is that it is restricted to families in a population-based cohort; vulnerable groups are under-represented. Nevertheless, our analysis suggests that interventions targeted at children experiencing four or more ACEs will not necessarily focus on the groups at highest risk of adverse outcomes. Our results underline the importance of the broader socioeconomic context for policies focused on ACEs.

Funding

Supported by a grant from the UK Economic and Social Research Council (ES/N000382/1).  相似文献   
32.
Employing liquid organic hydrogen carriers (LOHCs) to transport hydrogen to where it can be utilized relies on methods of efficient chemical dehydrogenation to access this fuel. Therefore, developing effective strategies to optimize the catalytic performance of cheap transition metal-based catalysts in terms of activity and stability for dehydrogenation of LOHCs is a critical challenge. Here, we report the design and synthesis of ultrasmall nickel nanoclusters (∼1.5 nm) deposited on defect-rich boron nitride (BN) nanosheet (Ni/BN) catalysts with higher methanol dehydrogenation activity and selectivity, and greater stability than that of some other transition-metal based catalysts. The interface of the two-dimensional (2D) BN with the metal nanoparticles plays a strong role both in guiding the nucleation and growth of the catalytically active ultrasmall Ni nanoclusters, and further in stabilizing these nanoscale Ni catalysts against poisoning by interactions with the BN substrate. We provide detailed spectroscopy characterizations and density functional theory (DFT) calculations to reveal the origin of the high productivity, high selectivity, and high durability exhibited with the Ni/BN nanocatalyst and elucidate its correlation with nanocluster size and support–nanocluster interactions. This study provides insight into the role that the support material can have both regarding the size control of nanoclusters through immobilization during the nanocluster formation and also during the active catalytic process; this twofold set of insights is significant in advancing the understanding the bottom-up design of high-performance, durable catalytic systems for various catalysis needs.

Driven by the environmental consequences of fossil energy consumption, hydrogen, a potentially renewable and sustainable resource for clean energy, has gradually evolved into an energetic area of research globally (13). In the hydrogen landscape, one of the key links bridging the gap between sustainable production and utilization is hydrogen storage and transportation (4, 5). In contrast to the conventional storage and transportation approaches of compressed gas, or solid-state storage, liquid organic hydrogen carriers (LOHCs), such as methanol (6, 7), have attracted significant attention. LOHCs are appealing due to their high gravimetric hydrogen content, relatively low cost, easy handling and transportation, as well as their ability to be manufactured from a variety of renewable sources (810). Based on this point, selective dehydrogenation of methanol by heterogeneous catalysts plays a vital role not only in fundamental research but also in practical industries. Currently, the noble-metal–based catalysts exhibit a high activity but are hindered by exorbitant pricing, low abundance, and susceptibility to CO poisoning (11, 12).Transition metal-based catalysts, by contrast, promise lower cost, but low activity and stability levels (mainly due to coke deposition and particle sintering) limit their potential deployment into dehydrogenation industries. Despite great efforts, developing effective strategies to greatly optimize the catalytic performance of cheaper transition metal-based catalysts, such as nickel-based catalysts for dehydrogenation of LOHCs, still remains a great, ongoing challenge (13, 14).Effective strategies to tune the catalytic properties of the transition metal-based catalysts is to take advantage of the size effect and metal–support interaction effect (1519). From the viewpoint of reactivity, ultrasmall nanoclusters are highly preferred as the reduction of the size significantly increases the amount of surface sites per unit weight and is a reliable method to produce more active catalysts. Thus, one of the most important objectives is to construct nanoclusters that are both small and monodisperse in size. However, the instability and aggregation of small nanocluster (sintering) affect their catalytic activity, consequently limiting the use for industrial applications. To overcome these drawbacks, design of a proper catalyst support was employed to suppress metal sintering and tremendously affect the catalytic properties of catalysts. The supports could not only help to disperse and anchor the nanoclusters, they also tremendously facilitate catalytic action and heighten overall performance by means of interacting with the metal nanoclusters (2027).By virtue of an exceptional chemical and thermal stability, large surface area, high thermal conductivity, and strong surface adsorbing capability, two-dimensional (2D) hexagonal BN nanosheets (h-BN or BN in this paper), a structural analog of graphene, are one of the most attractive transition metal catalysts supports (2830). The pristine BN surface is an inert support for metal nanoclusters, which would lead to catalyst deactivation by sintered metal species (31, 32). Thanks to the chemical modification/doping or defect engineering, BN owns greater possibilities in changing physical and chemical characteristics for catalysis development. However, the role of support in practical catalysts is still not clearly understood on various occasions as it is rather more complex (33). The size control of transition metal such as Ni is well known to be very sensitive to the preparation methods. Revealing the role of the support during the nanocluster formation and deposition is a prerequisite, and it may provide clues to an understanding of their role in subsequent catalytic processes.Therefore, here in this paper, we present surface-modified BN nanosheets with abundant O-terminated vacancies that not only play a vital role in promoting the one-pot synthesis of ultrasmall Ni nanoclusters (∼1.5 nm) with high catalytic activity, helping to disperse and anchor the nanoclusters, but that also strongly interact with these nanoclusters to enhance the sintering resistance and coke inhibition properties during the methanol dehydrogenation. We provide detailed spectroscopy characterizations and density functional theory (DFT) calculations to monitor the transformation of the BN nanosheets, which clarified the role of the substrate during the ultrasmall Ni nanoclusters formation and deposition. We found the Ni nanoclusters nucleation preferably takes place at the BN2O defects. A “pit” model structure was thus suggested for the Ni/BN system, in which the nanoclusters occupy pristine regions of the BN nanoflakes and interact with nearby BN edges, preserving the ultrasmall size of the nanoparticles. This facilitates their catalytic action in the process of methanol adsorption, CO and H2 transferring, endowing the catalysts with excellent selectivity, productivity, and stability performance. Besides, calculated turnover frequency (TOF) was found among the best compared with some other transition metal-based catalysts reported previously. Our discovery gives an understanding of the interfacial interaction between Ni nanoclusters and defect-rich BN nanosheet support both in the nanoclusters formation and catalytic process, which may enlighten the path of optimizing LOHC dehydrogenation research in the perspective of supported catalysts.  相似文献   
33.

Objective

The study was aimed at assessing the prevalence of compulsive exercising to control shape and weight in eating disorders (EDs) and its relationship with treatment outcome.

Method

Compulsive exercising to control shape and weight, defined according to a modified version of the Intense Exercising to Control Shape or Weight section of the Eating Disorder Examination (EDE), was assessed in 165 consecutive ED inpatients entering a protocol based on the transdiagnostic cognitive behavior theory and treatment of EDs. Baseline assessment also included anthropometry, the global EDE interview, the Beck Depression Inventory, the State-Trait Anxiety Inventory (STAI), the Eating Disorders Inventory-Perfectionism Scale, and the Temperament and Character Inventory.

Results

Of the patients, 45.5% were classified as compulsive exercisers, the prevalence being highest (80%) in restricting-type anorexia nervosa (AN), lowest in EDs not otherwise specified (31.9%), and intermediate in binge/purging AN (43.3%) and in purging-type bulimia nervosa (39.3%). Compulsive exercising to control shape and weight was independently predicted by the EDE restraint score (odds ratio, 1.32; 95% confidence interval, 1.06-1.64; P = .014) after adjustment for ED; the total amount of exercise was associated with EDE restraint, as well as with the Temperament and Character Inventory reward dependence. At follow-up, an improved EDE global score was predicted by lower baseline values, higher baseline STAI and STAI improvement, and lower amount of exercise in the last 4 weeks. Voluntary treatment discontinuation was not predicted by baseline exercise.

Discussion

Compulsive exercising to control shape and weight is a behavioral feature of restricting-type AN, associated with restraint and temperament dimensions, with influence on treatment outcome.  相似文献   
34.
Lung MRI for experimental drug research   总被引:1,自引:0,他引:1  
Current techniques to evaluate the efficacy of potential treatments for airways diseases in preclinical models are generally invasive and terminal. In the past few years, the flexibility of magnetic resonance imaging (MRI) to obtain anatomical and functional information of the lung has been explored with the scope of developing a non-invasive approach for the routine testing of drugs in models of airways diseases in small rodents. With MRI, the disease progression can be followed in the same animal. Thus, a significant reduction in the number of animals used for experimentation is achieved, as well as minimal interference with their well-being and physiological status. In addition, under certain circumstances the duration of the observation period after disease onset can be shortened since the technique is able to detect changes before these are reflected in parameters of inflammation determined using invasive procedures. The objective of this article is to briefly address MRI techniques that are being used in experimental lung research, with special emphasis on applications. Following an introduction on proton techniques and MRI of hyperpolarized gases, the attention is shifted to the MRI analysis of several aspects of lung disease models, including inflammation, ventilation, emphysema, fibrosis and sensory nerve activation. The next subject concerns the use of MRI in pharmacological studies within the context of experimental lung research. A final discussion points towards advantages and limitations of MRI in this area.  相似文献   
35.
目的探讨细胞间隙连接蛋白(connexin 43,Cx43)在(Brown Norway,BN)大鼠视网膜中的分布特点以及氪激光损伤视网膜后Cx43分布的变化。方法应用雄性BN为研究对象,氪红激光眼底光凝(波长647nm,能量360mw,光斑直径50μm,曝光0.05s)?右眼视盘周围10个激光点。光凝后1周开始取材,应用免疫组化方法观察Cx43在BN大鼠视网膜中的分布特点。结果正常视网膜内界膜、视神经纤维层以及神经节细胞层明显表达,神经节细胞表达的主要位置是细胞浆和细胞膜,色素上皮细胞全层表达,内外颗粒层及内外丛状层无表达。激光损伤后的内界膜,视神经纤维层以及神经节细胞层Cx43表达明显减少,瘢痕区视网膜色素上皮细胞接近消失,而激光斑周边色素上皮细胞表达不受影响,激光斑部位增殖的成纤维样细胞部分表达。结论正常视网膜的Cx43主要分布在内界膜、神经纤维层、视网膜节细胞层和视网膜色素上皮层,激光损伤后内界膜、视神经纤维层以及神经节细胞层表达减弱,激光斑周围色素上皮细胞中表达无明显变化,激光损伤瘢痕中的成纤维细胞有少量表达。  相似文献   
36.
BN3C对大鼠心肌细胞膜二氢吡啶受体的作用   总被引:3,自引:0,他引:3  
目的研究BN3C对大鼠心肌细胞膜二氢吡啶受体的作用。方法放射性配基结合实验。结果[3H]PN200-110在0.1~3.2nmol·L-1范围与大鼠心肌细胞膜的特异性结合是可饱和的,其KD和Bmax值分别为0.82nmol·L-1和109.72pmol·g-1Pro-1。当有1×10-9mol·L-1BN3C存在时,其KD和Bmax值分别为2.01nmol·L-1和115.31pmol·g-1Pro-1。BN3C、拉西地平、硝苯吡啶竞争性抑制[3H]PN200-110与大鼠心肌细胞膜结合的IC50分别为2.4×10-9,1.5×10-8,1.9×10-8nmol·L-1;KI值分别为1.49,9.22和11.64nmol·L-1。结论BN3C可特异性地作用于[3H]PN200-110的结合部位,竞争性地抑制[3H]PN200-110与大鼠心肌细胞膜的结合;BN3C与受体的亲和力强于拉西地平和硝苯吡啶。  相似文献   
37.
A simple inexpensive, and rapid method for inducing large volumes of ascitic fluid in rats is described. The procedure involves intraperitoneal injections of Freund's adjuvant emulsion on alternate days. Antibody activity of the ascitic fluid approximates that found in the serum. Female rats consistently respond better than males. Members of all 9 strains of rats tested produced ascites using this procedure.  相似文献   
38.
The development of drug resistance is an important factor contributing to failure of chemotherapy in cancer patients. Cyclophosphamide (CP) is a cytostatic drug widely used in the treatment of haematological malignancies and solid tumours. Because CP requires bioactivation to become cytotoxic, an in vivo approach was chosen to generate a subline of the Brown Norway rat acute myelocytic leukaemia (BNML/CPR) highly resistant to CP to serve as a model to investigate the molecular mechanism(s) of cyclophosphamide resistance. The role of the CP-detoxifying enzyme aldehyde dehydrogenase (ALDH) in the molecular mechanism of CP resistance in this subline of the BNML has been investigated. Compared to the parent BNML cell line, the BNML/CPR cell line displayed an approximately 6-fold higher level of ALDH enzyme activity. Pretreatment of leukaemic rats with the ALDH inhibitor disulfiram resulted in a restoration of CP sensitivity of animals carrying the BNML/CPR cells. Furthermore, in vitro incubation of BNML/CPR cells with disulfiram prior to incubation with the activated CP derivative mafosfamide resulted in an extra 2–3 log cell kill as indicated by the survival time of rats which were injected with disulfiram pretreated BNML/CPR cells compared to non-pretreated BNML/CPR cells. Data on the glutathione S-transferases (GSTs) isozyme profiles of cytoplasmic liver and spleen extracts of BNML- and BNML/CPR-carrying leukaemic rats indicated that the total GST enzyme amount was lower in BNML/CPR cells than in parent BNML cells. Furthermore, the BNML/CPR subline proved to be sensitive to phosphoramide mustard, both in vivo and in vitro.  相似文献   
39.
Conditions for in vitro long-term maintenance and proliferation of the Brown Norway (BN) rat myelocytic leukemia cell (BNML) are described. During a primary culture of leukemic rat marrow, a few leukemic cells proliferated and were initially dependent on an adherent cell population but later acquired the capability of independent growth. A wild BN leukemic stem cell line has been maintained in vitro for several months, without noticeable phenotypic alterations. The doubling time of the cultured cells was 40 h. The cells were promyelocytes. The cytochemical markers of the original BN leukemia cells were preserved. The cultured cell line transferred leukemia exclusively to BN rats. Wistar and BDIX rats were resistant. The virulence of cultured leukemic cell was measured by shortened survival times after transplantation in animals of a fixed number of leukemic cells. The role of bone marrow microenvironment in the initiation of long-term growth is discussed.  相似文献   
40.
Rationale: Platelet-activating factor (PAF) is a membrane-derived phospholipid mediator that has biological effects on a variety of cells and tissues. A variety of stimuli, including those producing inflammation, promote the synthesis and release of PAF from various cell types. Evidence suggests that PAF exerts cellular actions through a plasma membrane receptor as well as via intracellular (microsomal) PAF binding sites. Objective: The present study was designed to: 1) investigate the role of PAF in a model of inflammatory nociception in rats (i.e. the formalin test), and 2) localize PAF's site(s) of action in nociception. To do this, we assessed the effect of administering two PAF antagonists (BN 52021 and BN 50730, which are selective for cell surface and intracellular PAF binding sites, respectively) on formalin-induced nociceptive responses. Methods: Forty minutes prior to formalin injection into the rat hindpaw, male Sprague-Dawley rats received systemic injections of BN 52021 (10, 1, or 0.1 mg/kg), BN 50730 (10, 1, or 0.1 mg/kg), or vehicle (45% 2-hydroxypropyl-β-cyclodextrin in distilled water, HBC) and the effects of the drugs on nociceptive behavioral responses were measured. Results: Rats receiving systemic BN 52021 or BN 50730 displayed a significant reduction of nociceptive responses in the late, but not early, phase of formalin-induced nociception. Conclusions: These findings suggest a role for endogenous PAF in nociceptive transmission, especially for persistent pain such as that which occurs in the late phase of the formalin test. The findings also indicate that both intracellular and cell surface PAF binding sites are involved in nociceptive modulation in rats, and that PAF antagonists might be useful for treating some patients with acute or chronic pain. Electronic Publication  相似文献   
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