全文获取类型
收费全文 | 1260篇 |
免费 | 158篇 |
国内免费 | 1篇 |
出版年
2021年 | 24篇 |
2018年 | 19篇 |
2017年 | 17篇 |
2016年 | 22篇 |
2015年 | 40篇 |
2014年 | 38篇 |
2013年 | 65篇 |
2012年 | 69篇 |
2011年 | 55篇 |
2010年 | 28篇 |
2009年 | 32篇 |
2008年 | 59篇 |
2007年 | 51篇 |
2006年 | 32篇 |
2005年 | 44篇 |
2004年 | 33篇 |
2003年 | 35篇 |
2002年 | 33篇 |
2001年 | 40篇 |
2000年 | 25篇 |
1999年 | 27篇 |
1998年 | 11篇 |
1997年 | 28篇 |
1996年 | 16篇 |
1995年 | 13篇 |
1994年 | 11篇 |
1993年 | 10篇 |
1992年 | 21篇 |
1991年 | 35篇 |
1990年 | 12篇 |
1989年 | 27篇 |
1988年 | 18篇 |
1987年 | 26篇 |
1986年 | 27篇 |
1985年 | 24篇 |
1984年 | 21篇 |
1982年 | 16篇 |
1981年 | 16篇 |
1980年 | 11篇 |
1979年 | 11篇 |
1978年 | 15篇 |
1977年 | 21篇 |
1975年 | 10篇 |
1974年 | 14篇 |
1972年 | 18篇 |
1971年 | 12篇 |
1969年 | 13篇 |
1968年 | 12篇 |
1967年 | 10篇 |
1965年 | 10篇 |
排序方式: 共有1419条查询结果,搜索用时 109 毫秒
151.
Song F Holland R Barton GR Bachmann M Blyth A Maskrey V Aveyard P Sutton S Leonardi-Bee J Brandon TH 《Trials》2012,13(1):69
ABSTRACT: BACKGROUND: Most people who stop smoking successfully for a few weeks will return to smoking again in the medium term. There are few effective interventions to prevent this relapse and none used routinely in clinical practice. A previous exploratory meta-analysis suggested that self-help booklets may be effective but requires confirmation. This trial aims to evaluate the effectiveness and cost-effectiveness of a set of self-help educational materials to prevent smoking relapse in the NHS Stop Smoking Service. METHODS: This is an open, randomised controlled trial. The target population is carbon monoxide (CO) verified quitters at 4 weeks in the NHS stop smoking clinic (total sample size N=1,400). The experimental intervention tested is a set of 8 revised Forever Free booklets, including an introduction booklet and more extensive information on all important issues for relapse prevention. The control intervention is a leaflet that has no evidence to suggest it is effective but is currently given to some patients using NHS stop smoking services. Two follow-up telephone interviews will be conducted at 3 and 12 months after quit date. The primary outcome will be prolonged abstinence from months 4-12 with no more than 5 lapses, confirmed by carbon monoxide test at 12 month assessment. The secondary outcomes will be 7-day self-report point prevalence abstinence at 3 months and 7-day biochemically confirmed point prevalence abstinence at 12 months. To assess cost-effectiveness, costs will be estimated from a health service perspective and the EQ-5D will be used to estimate the QALY (Quality Adjusted Life Year) gain associated with each intervention. The comparison of smoking abstinence rates (and any other binary outcomes) between the two trial arms will be carried out using odds ratio as the outcome statistic and other related statistical tests. Exploratory subgroup analyses, including logistic regression analyses with interaction terms, will be conducted to investigate possible effect modifying variables. DISCUSSION: The possible effect of self-help educational materials for the prevention of smoking relapse has important public health implications. Trial Registration: Current Controlled Trials ISRCTN36980856. 相似文献
152.
We investigated the ability of western equine encephalitis virus envelope glycoproteins (WEEV GP) to pseudotype lentiviral vectors. The titers of WEEV GP-pseudotyped human immunodeficiency virus type 1 (HIV) ranged as high as 8.0 × 104 IU/ml on permissive cells. Sera from WEEV-infected mice specifically neutralized these pseudotypes; cell transduction was also sensitive to changes in pH. The host range of the pseudotyped particles in vitro was somewhat limited, which is atypical for most alphaviruses. HIV vectors pseudotyped by WEEV GP may be a useful tool for characterizing WEEV cell binding and entry and screening for small-molecule inhibitors. 相似文献
153.
Kraft Z Strouss K Sutton WF Cleveland B Tso FY Polacino P Overbaugh J Hu SL Stamatatos L 《Journal of virology》2008,82(12):5912-5921
The vast majority of studies with candidate immunogens based on the human immunodeficiency virus envelope (Env) have been conducted with Env proteins derived from clade B viruses isolated during chronic infection. Whether non-clade B Env protein immunogens will elicit antibodies with epitope specificities that are similar to those of antibodies elicited by clade B Envs and whether the antibodies elicited by Envs derived from early transmitted viruses will be similar to those elicited by Envs derived from viruses isolated during chronic infection are currently unknown. Here we performed immunizations with four clade A Envs, cloned directly from the peripheral blood of infected individuals during acute infection, which differed in lengths and extents of glycosylation. The antibody responses elicited by these four Envs were compared to each other and to those elicited by a well-characterized clade B Env immunogen derived from the SF162 virus, which was isolated during chronic infection. Only one clade A Env, the one with the fewer glycosylation sites, elicited homologous neutralizing antibodies (NAbs); these did not target the V1, V2, or V3 regions. In contrast, all four clade A Envs elicited anti-V3 NAbs against "easy-to-neutralize" clade B and clade A isolates, irrespective of the variable region length and extent of glycosylation of the Env used as an immunogen. These anti-V3 NAbs did not access their epitopes on homologous and heterologous clade A, or B, neutralization-resistant viruses. The length and extent of glycosylation of the variable regions on the clade A Env immunogens tested did not affect the breadth of the elicited NAbs. Our data also indicate that the development of cross-reactive NAbs against clade A viruses faces similar hurdles to the development of cross-reactive anti-clade B NAbs. 相似文献
154.
Reproductive biology of blue sucker in a large Midwestern river 总被引:1,自引:0,他引:1
D. J. Daugherty T. D. Bacula T. M. Sutton 《Zeitschrift fur angewandte Ichthyologie》2008,24(3):297-302
Efforts to protect or rehabilitate depressed blue sucker Cycleptus elongatus populations require an understanding of life‐history characteristics and reproductive biology to provide fisheries managers with the tools required for science‐based management. The objective of this study was to examine the reproductive biology of blue sucker in the Wabash River, Indiana, during March and April 2006. A total of 105 reproductively mature blue sucker (53 males, 52 females) was collected using boat electrofishing to examine size‐at‐maturity, absolute fecundity, gonadosomatic index (GSI), relative fecundity, and estimated egg size. Size‐at‐maturity was estimated at 515 mm total length (TL) for males and 568 mm TL for females. Mean absolute fecundity of females captured during the study was 150 704 eggs per female (range, 26 829–267 471 eggs per female) and was positively related to both TL (r2 = 0.66) and wet weight (r2 = 0.77). Mean GSI was 6.4% (range, 2–9.3%) for males and 17.2% (range, 4.3–23.4%) for females. Relative fecundity ranged from 15 331 to 65 887 eggs kg?1 body weight (mean = 46 946 eggs kg?1 body weight) and was strongly correlated with GSI (r2 = 0.87). Mean estimated egg size was 278 eggs g?1 (range, 229 364 eggs g?1) and exhibited an inverse relationship to GSI (r2 = 0.42). The results of our study provide information on the reproductive biology of blue sucker which can be used to aid in the identification of potential recovery threats for depressed populations. 相似文献
155.
Melanocortin receptors are considered promising candidates for the treatment of behavioral and metabolic disorders ranging from obesity to anorexia and cachexia. These experiments examined the response of mice to peripheral injections of two compounds. PG932 is a derivative of SHU9119 which is non-selective antagonist of melanocortin-3 and melanocortin-4 receptors (Mc3r and Mc4r). PG946 is a derivative of a hybrid of alpha- and beta-MSH, and is a moderately selective Mc3r antagonist. SHU9119 increases food intake when administered intracerebroventricularly but is without effect when injected into the periphery. In contrast, PG932 was found to be highly effective at stimulating food intake when administered peripherally by intraperitoneal injection. The orexigenic effect of PG932 required functional Mc4r, suggesting that inhibition of this receptor is involved in the stimulation of food intake. PG946 did not significantly affect on feeding behavior. PG932 is thus a useful new compound for studies examining the regulation of appetite and energy balance, and may also prove useful for the treatment of cachectic conditions. 相似文献
156.
Although rodent models are very popular for scientific studies, it is becoming more evident that large animal models can provide unique opportunities for biomedical research. Sheep are docile in nature and large in size, which facilitates surgical manipulation, and their physiology is similar to humans. As a result, for decades they have been chosen for several models and continue to be used to study an ever-increasing array of applications. Despite this, their full potential has not been exploited. Here, we review the use of sheep as an animal model for human vaccine development, asthma pathogenesis and treatment, the study of neonatal development, and the optimization of drug delivery and surgical techniques. 相似文献
157.
Differential uptake and translocation of Ca and Sr in organisms have been reported, calling into question the use of Sr to
track Ca cycling in the environment. We investigated the relationship between Ca/Sr ratios in soil extracts of various strengths
(H2O, NH4Cl, and NH4EDTA) and seedlings of sugar maple (Acer saccharum Marsh.) grown from natural regeneration on 37 sites. Our objectives were to determine if Ca/Sr ratios in soil extracts are
correlated with those in sugar maple tissues, and what soil extractant best duplicate plant tissue Ca/Sr ratios. Leaves had
higher Ca/Sr ratios than stems and the extractants did not produce equal Ca/Sr ratios: H2O had the lowest Ca/Sr, and NH4EDTA the highest. The relationships between soil extract Ca/Sr ratios and leaf and stem Ca/Sr ratios were significant and
linear, but the slopes differed among extractants. The lowest slope (0.45) was observed for the water extract/leaves and the
highest (2.15) for the NH4EDTA extract/stem with discrimination factors ranging from 0.22 with NH4EDTA to 1.59 for water. Leaf extracts were more strongly correlated with soil Ca/Sr than stem extracts (R
2 of 0.57–0.7 vs. R
2 of 0.45–0.6, respectively). These findings support the use of Ca/Sr ratios in plants to track their source of soil Ca, but
they highlight the need to calibrate the relationships for the plant tissue and soil extractant used. 相似文献
158.
Karagiannis SN Bracher MG Beavil RL Beavil AJ Hunt J McCloskey N Thompson RG East N Burke F Sutton BJ Dombrowicz D Balkwill FR Gould HJ 《Cancer immunology, immunotherapy : CII》2008,57(2):247-263
Antibodies directed against tumor-associated antigens are emerging as effective treatments for a number of cancers, although
the mechanism(s) of action for some are unclear and still under investigation. We have previously examined a chimeric IgE
antibody (MOv18 IgE), against the ovarian tumor-specific antigen, folate binding protein (FBP), and showed that it can direct
human PBMC to kill ovarian cancer cells. We have developed a three-color flow cytometric assay to investigate the mechanism
by which IgE receptors on U937 monocytes target and kill ovarian tumor cells. U937 monocytes express three IgE receptors,
the high-affinity receptor, FcεRI, the low-affinity receptor, CD23, and galectin-3, and mediate tumor cell killing in vitro
by two mechanisms, cytotoxicity, and phagocytosis. Our results suggest that CD23 mediates phagocytosis, which is enhanced
by upregulation of CD23 on U937 cells with IL-4, whereas FcεRI mediates cytotoxicity. We show that effector : tumor cell bridging
is associated with both activities. Galectin-3 does not appear to be involved in tumor cell killing. U937 cells and IgE exerted
ovarian tumor cell killing in vivo in our xenograft model in nude mice. Harnessing IgE receptors to target tumor cells suggests
the potential of tumor-specific IgE antibodies to activate effector cells in immunotherapy of ovarian cancer.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
159.
Babu Kunadian Joel Dunning Anthony P Roberts Robert Morley Darragh Twomey James A Hall Andrew G C Sutton Robert A Wright Douglas F Muir Mark A de Belder 《BMJ (Clinical research ed.)》2008,336(7650):931-934
Objective To use funnel plots and cumulative funnel plots to compare in-hospital outcome data for operators undertaking percutaneous coronary interventions with predicted results derived from a validated risk score to allow for early detection of variation in performance.Design Analysis of prospectively collected data.Setting Tertiary centre NHS hospital in the north east of England.Participants Five cardiologists carrying out percutaneous coronary interventions between January 2003 and December 2006.Main outcome measures In-hospital major adverse cardiovascular and cerebrovascular events (in-hospital death, Q wave myocardial infarction, emergency coronary artery bypass graft surgery, and cerebrovascular accident) analysed against the logistic north west quality improvement programme predicted risk, for each operator. Results are displayed as funnel plots summarising overall performance for each operator and cumulative funnel plots for an individual operator’s performance on a case series basis.Results The funnel plots for 5198 patients undergoing percutaneous coronary interventions showed an average observed rate for major adverse cardiovascular and cerebrovascular events of 1.96% overall. This was below the predicted risk of 2.06% by the logistic north west quality improvement programme risk score. Rates of in-hospital major adverse cardiovascular and cerebrovascular events for all operators were within the 3σ upper control limit of 2.75% and 2σ upper warning limit of 2.49%.Conclusion The overall in-hospital major adverse cardiovascular and cerebrovascular events rates were under the predicted event rate. In-hospital rates after percutaneous coronary intervention procedure can be monitored successfully using funnel and cumulative funnel plots with 3σ control limits to display and publish each operator’s outcomes. The upper warning limit (2σ control limit) could be used for internal monitoring. The main advantage of these charts is their transparency, as they show observed and predicted events separately. By this approach individual operators can monitor their own performance, using the predicted risk for their patients but in a way that is compatible with benchmarking to colleagues, encapsulated by the funnel plot. This methodology is applicable regardless of variations in individual operator case volume and case mix. 相似文献
160.