全文获取类型
收费全文 | 4340篇 |
免费 | 315篇 |
国内免费 | 1篇 |
专业分类
4656篇 |
出版年
2023年 | 19篇 |
2022年 | 40篇 |
2021年 | 106篇 |
2020年 | 64篇 |
2019年 | 81篇 |
2018年 | 107篇 |
2017年 | 90篇 |
2016年 | 146篇 |
2015年 | 194篇 |
2014年 | 228篇 |
2013年 | 257篇 |
2012年 | 403篇 |
2011年 | 355篇 |
2010年 | 236篇 |
2009年 | 176篇 |
2008年 | 259篇 |
2007年 | 275篇 |
2006年 | 269篇 |
2005年 | 197篇 |
2004年 | 225篇 |
2003年 | 207篇 |
2002年 | 189篇 |
2001年 | 32篇 |
2000年 | 30篇 |
1999年 | 45篇 |
1998年 | 54篇 |
1997年 | 44篇 |
1996年 | 29篇 |
1995年 | 41篇 |
1994年 | 25篇 |
1993年 | 17篇 |
1992年 | 21篇 |
1991年 | 22篇 |
1990年 | 28篇 |
1989年 | 13篇 |
1988年 | 16篇 |
1987年 | 11篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 9篇 |
1983年 | 13篇 |
1982年 | 3篇 |
1981年 | 12篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1975年 | 12篇 |
1973年 | 4篇 |
1972年 | 2篇 |
排序方式: 共有4656条查询结果,搜索用时 0 毫秒
151.
Free RB Hazelwood LA Cabrera DM Spalding HN Namkung Y Rankin ML Sibley DR 《The Journal of biological chemistry》2007,282(29):21285-21300
As for all proteins, G protein-coupled receptors (GPCRs) undergo synthesis and maturation within the endoplasmic reticulum (ER). The mechanisms involved in the biogenesis and trafficking of GPCRs from the ER to the cell surface are poorly understood, but they may involve interactions with other proteins. We have now identified the ER chaperone protein calnexin as an interacting protein for both D(1) and D(2) dopamine receptors. These protein-protein interactions were confirmed using Western blot analysis and co-immunoprecipitation experiments. To determine the influence of calnexin on receptor expression, we conducted assays in HEK293T cells using a variety of calnexin-modifying conditions. Inhibition of glycosylation either through receptor mutations or treatments with glycosylation inhibitors partially blocks the interactions with calnexin with a resulting decrease in cell surface receptor expression. Confocal fluorescence microscopy reveals the accumulation of D(1)-green fluorescent protein and D(2)-yellow fluorescent protein receptors within internal stores following treatment with calnexin inhibitors. Overexpression of calnexin also results in a marked decrease in both D(1) and D(2) receptor expression. This is likely because of an increase in ER retention because confocal microscopy revealed intracellular clustering of dopamine receptors that were co-localized with an ER marker protein. Additionally, we show that calnexin interacts with the receptors via two distinct mechanisms, glycan-dependent and glycan-independent, which may underlie the multiple effects (ER retention and surface trafficking) of calnexin on receptor expression. Our data suggest that optimal receptor-calnexin interactions critically regulate D(1) and D(2) receptor trafficking and expression at the cell surface, a mechanism likely to be of importance for many GPCRs. 相似文献
152.
Huang Y Qiu J Dong S Redell MS Poli V Mancini MA Tweardy DJ 《The Journal of biological chemistry》2007,282(48):34958-34967
153.
154.
Levine MD Klem ML Kalarchian MA Wing RR Weissfeld L Qin L Marcus MD 《Obesity (Silver Spring, Md.)》2007,15(5):1267-1277
Objective: Women 25 to 45 years old are at risk for weight gain and future obesity. This trial was designed to evaluate the efficacy of two interventions relative to a control group in preventing weight gain among normal or overweight women and to identify demographic, behavioral, and psychosocial factors related to weight gain prevention. Research Methods and Procedures: Healthy women (N = 284), ages 25 to 44, with BMI < 30 were randomized to one of three intervention conditions: a clinic‐based group, a correspondence course, or an information‐only control. Intervention was provided over 2 years, with a follow‐up at Year 3. BMI and factors related to eating and weight were assessed yearly. Results: Over the 3‐year study period, 40% (n = 114) of the women remained at or below baseline body weight (±2 lbs), and 60% gained weight (>2 lbs). Intervention had no effect on weight over time. Independently of intervention, women who were older, not actively dieting to lose weight, and who reported less perceived hunger at baseline were more likely to be successful at weight maintenance. Weight maintenance also was associated with increasing dietary restraint (conscious thoughts and purposeful behaviors to control calorie intake) and decreasing dietary disinhibition (the tendency to lose control over eating) over time. Discussion: This study raises concern about the feasibility and efficacy of weight gain prevention interventions because most women were interested in weight loss, rather than weight gain prevention, and the interventions had no effect on weight stability. Novel approaches to the prevention of weight gain are needed. 相似文献
155.
Núñez NP Carpenter CL Perkins SN Berrigan D Jaque SV Ingles SA Bernstein L Forman MR Barrett JC Hursting SD 《Obesity (Silver Spring, Md.)》2007,15(8):1980-1987
Objective: To evaluate the effects of body adiposity on bone mineral density in the presence and absence of ovarian hormones in female mice and postmenopausal women. Research Methods and Procedures: We assessed percentage body fat, serum leptin levels, and bone mineral density in ovariectomized and non‐ovariectomized C57BL/6 female mice that had been fed various calorically dense diets to induce body weight profiles ranging from lean to very obese. Additionally, we assessed percentage body fat and whole body bone mineral density in 37 overweight and extremely obese postmenopausal women from the Women's Contraceptive and Reproductive Experiences study. Results: In mice, higher levels of body adiposity (>40% body fat) were associated with lower bone mineral density in ovariectomized C57BL/6 female mice. A similar trend was observed in a small sample of postmenopausal women. Discussion: The complementary studies in mice and women suggest that extreme obesity in postmenopausal women may be associated with reduced bone mineral density. Thus, extreme obesity (BMI > 40 kg/m2) may increase the risk for osteopenia and osteoporosis. Given the obesity epidemic in the U.S. and in many other countries, and, in particular, the rising number of extremely obese adult women, increased attention should be drawn to the significant and interrelated public health issues of obesity and osteoporosis. 相似文献
156.
Cooley M Carychao D Crawford-Miksza L Jay MT Myers C Rose C Keys C Farrar J Mandrell RE 《PloS one》2007,2(11):e1159
Fresh vegetables have become associated with outbreaks caused by Escherichia coli O157:H7 (EcO157). Between 1995-2006, 22 produce outbreaks were documented in the United States, with nearly half traced to lettuce or spinach grown in California. Outbreaks between 2002 and 2006 induced investigations of possible sources of pre-harvest contamination on implicated farms in the Salinas and San Juan valleys of California, and a survey of the Salinas watershed. EcO157 was isolated at least once from 15 of 22 different watershed sites over a 19 month period. The incidence of EcO157 increased significantly when heavy rain caused an increased flow rate in the rivers. Approximately 1000 EcO157 isolates obtained from cultures of>100 individual samples were typed using Multi-Locus Variable-number-tandem-repeat Analysis (MLVA) to assist in identifying potential fate and transport of EcO157 in this region. A subset of these environmental isolates were typed by Pulse Field Gel Electrophoresis (PFGE) in order to make comparisons with human clinical isolates associated with outbreak and sporadic illness. Recurrence of identical and closely related EcO157 strains from specific locations in the Salinas and San Juan valleys suggests that transport of the pathogen is usually restricted. In a preliminary study, EcO157 was detected in water at multiple locations in a low-flow creek only within 135 meters of a point source. However, possible transport up to 32 km was detected during periods of higher water flow associated with flooding. During the 2006 baby spinach outbreak investigation, transport was also detected where water was unlikely to be involved. These results indicate that contamination of the environment is a dynamic process involving multiple sources and methods of transport. Intensive studies of the sources, incidence, fate and transport of EcO157 near produce production are required to determine the mechanisms of pre-harvest contamination and potential risks for human illness. 相似文献
157.
Parent overweight predicts daughters' increase in BMI and disinhibited overeating from 5 to 13 years
Objective: To assess whether parental overweight status and disinhibited overeating are predictive of daughters’ accelerated weight gain and disinhibited overeating. Research Methods and Procedures: Participants were part of a longitudinal study of girls (N = 197) and their parents. Measured height and weight were used to calculate BMI [weight (kilograms)/height (meters)2]. Parents’ disinhibited eating behavior was assessed using the Eating Inventory. Girls’ disinhibited eating was assessed using a behavioral protocol to measure eating in the absence of hunger. Girls were classified based on parental overweight at study entry into four groups: neither, mother only, father only, or both parents overweight. Results: Girls with both parents overweight had the most rapid increases in BMI from 5 to 13 years of age; BMI increased most slowly among the neither parent overweight group, with intermediate increases in BMI among mother only and father only overweight groups. Daughters with both parents overweight at study entry were eight times more likely to be overweight at age 13, controlling for daughters’ weight at age 5. Girls with both parents overweight had higher levels of disinhibited eating across all ages than all other groups. Although girls in all parental weight status groups showed increases in disinhibited eating over time, girls with both parents overweight had larger increases in disinhibited eating over time compared with all other groups. Discussion: Girls growing up in families differing in parental overweight had divergent developmental trajectories for BMI and disinhibited overeating. Findings reveal the need to focus prevention efforts on overweight parents of young children. 相似文献
158.
Michele T Guerin Wayne Martin Jarle Reiersen Olaf Berke Scott A McEwen Jean-Robert Bisaillon Ruff Lowman 《BMC veterinary research》2007,3(1):1-12
Background
The most predominant beta2-integrin lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, alphaLbeta2), expressed on all leukocytes, is essential for many adhesive functions of the immune system. Interestingly, RTX toxin-producing bacteria specifically target this leukocyte beta2-integrin which exacerbates lesions and disease development.Results
This study reports the sequencing of the wild boar beta2-integrin CD11a and CD18 cDNAs. Predicted CD11a and CD18 subunits share all the main structural characteristics of their mammalian homologues, with a larger interspecies conservation for the CD18 than the CD11a. Besides these strong overall similarities, wild boar and domestic pig LFA-1 differ by 2 (CD18) and 1 or 3 (CD11a) substitutions, of which one is located in the crucial I-domain (CD11a, E168D).Conclusion
As most wild boars are seropositive to the RTX toxin-producing bacterium Actinobacillus pleuropneumoniae and because they have sustained continuous natural selection, future studies addressing the functional impact of these polymorphisms could bring interesting new information on the physiopathology of Actinobacillus pleuropneumoniae-associated pneumonia in domestic pigs. 相似文献159.
160.