全文获取类型
收费全文 | 2679篇 |
免费 | 272篇 |
国内免费 | 2篇 |
专业分类
2953篇 |
出版年
2024年 | 2篇 |
2023年 | 15篇 |
2022年 | 42篇 |
2021年 | 64篇 |
2020年 | 43篇 |
2019年 | 49篇 |
2018年 | 49篇 |
2017年 | 47篇 |
2016年 | 83篇 |
2015年 | 157篇 |
2014年 | 196篇 |
2013年 | 174篇 |
2012年 | 283篇 |
2011年 | 281篇 |
2010年 | 166篇 |
2009年 | 134篇 |
2008年 | 199篇 |
2007年 | 165篇 |
2006年 | 160篇 |
2005年 | 157篇 |
2004年 | 136篇 |
2003年 | 104篇 |
2002年 | 102篇 |
2001年 | 15篇 |
2000年 | 5篇 |
1999年 | 12篇 |
1998年 | 27篇 |
1997年 | 9篇 |
1996年 | 9篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有2953条查询结果,搜索用时 15 毫秒
51.
Kristin A. Trott Amy Richardson Michael A. Hudgens Kristina Abel 《Journal of virology》2013,87(17):9523-9537
Human immunodeficiency virus (HIV) is characterized by immune activation, while chronic malaria is associated with elevated interleukin-10 (IL-10) levels. How these apparently antagonizing forces interact in the coinfected host is poorly understood. Using a rhesus macaque model of simian immunodeficiency virus (SIV)-Plasmodium fragile coinfection, we evaluated how innate immune effector cells affect the balance between immune activation and regulation. In vitro Toll-like receptor (TLR) responses of peripheral blood myeloid dendritic cells (mDC) and monocytes were temporarily associated with acute parasitemic episodes and elevated plasma IL-10 levels. Prolonged infection resulted in a decline of mDC function. Monocytes maintained TLR responsiveness but, in addition to IL-12 and tumor necrosis factor alpha, also produced IL-10. Consistent with the role of spleen in the clearance of parasite-infected red blood cells, coinfected animals also had increased splenic IL-10 mRNA levels. The main cellular source of IL-10 in the spleens of coinfected animals, however, was not splenic macrophages but T cells, suggesting an impairment of adaptive immunity. In contrast to those in spleen, IL-10-positive cells in axillary lymph nodes of coinfected animals were predominantly mDC, reminiscent of the immunosuppressive phenotype of peripheral blood mDC. Concurrent with IL-10 induction, however, SIV infection promoted elevated systemic IL-12 levels. The continuously increasing ratio of plasma IL-12 to IL-10 suggested that the overall host response in SIV-P. fragile-coinfected animals was shifted toward immune activation versus immune regulation. Therefore, SIV-P. fragile coinfection might be characterized by earlier manifestation of immune dysfunction and exhaustion than that of single-pathogen infections. This could translate into increased morbidity in HIV-malaria-coinfected individuals. 相似文献
52.
53.
Bark beetle infestation impacts on nutrient cycling, water quality and interdependent hydrological effects 总被引:1,自引:0,他引:1
Kristin M. Mikkelson Lindsay A. Bearup Reed M. Maxwell John D. Stednick John E. McCray Jonathan O. Sharp 《Biogeochemistry》2013,115(1-3):1-21
Bark beetle populations have drastically increased in magnitude over the last several decades leading to the largest-scale tree mortality ever recorded from an insect infestation on multiple wooded continents. When the trees die, the loss of canopy and changes in water and nutrient uptake lead to observable changes in hydrology and biogeochemical cycling. This review aims to synthesize the current research on the effects of the bark beetle epidemic on nutrient cycling and water quality while integrating recent and relevant hydrological findings, along with suggesting necessary future research avenues. Studies generally agree that snow depth will increase in infested forests, though the magnitude is uncertain. Changes in evapotranspiration are more variable as decreased transpiration from tree death may be offset by increased understory evapotranspiration and ground evaporation. As a result of such competing hydrologic processes that can affect watershed biogeochemistry along with the inherent variability of natural watershed characteristics, water quality changes related to beetle infestation are difficult to predict and may be regionally distinct. However, tree-scale changes to soil–water chemistry (N, P, DOC and base cation concentrations and composition) are being observed in association with beetle outbreaks which ultimately could lead to larger-scale responses. The different temporal and spatial patterns of bark beetle infestations due to different beetle and tree species lead to inconsistent infestation impacts. Climatic variations and large-scale watershed responses provide a further challenge for predictions due to spatial heterogeneities within a single watershed; conflicting reports from different regions suggest that hydrologic and water quality impacts of the beetle on watersheds cannot be generalized. Research regarding the subsurface water and chemical flow-paths and residence times after a bark beetle epidemic is lacking and needs to be rigorously addressed to best predict watershed or regional-scale changes to soil–water, groundwater, and stream water chemistry. 相似文献
54.
Dana R. Warren Kristin E. Judd Darren L. Bade Gene E. Likens Clifford E. Kraft 《Hydrobiologia》2013,717(1):119-131
Forested headwater streams play an important role in watershed nutrient dynamics, and wood is thought to be a key factor influencing habitat structure and nitrate-nitrogen dynamics in many forested streams. Because wood in streams can promote nitrogen uptake through denitrification, we hypothesized that nitrate uptake velocities would decrease following wood removal. We measured stream characteristics and nitrate uptake velocities before and after wood manipulation experiments conducted at Hubbard Brook Experimental Forest, NH, and the Sleepers River watershed, VT. The mean size of stream substrates and the amount of riffle habitat increased following wood removal. In contrast to our expectations, summer nitrate uptake velocities increased in the wood removal treatments relative to the reference treatments, possibly because wood removal increased the availability of stable substrates for periphyton growth, therefore increasing nitrate demand in these streams. Our results highlight that effects of wood on stream ecosystems occur through multiple pathways and suggest that the relative importance of these pathways may vary seasonally. 相似文献
55.
Andrew R. Williams Sara E. Zakutansky Kazutoyo Miura Matthew D.J. Dicks Thomas S. Churcher Kerry E. Jewell Aisling M. Vaughan Alison V. Turner Melissa C. Kapulu Kristin Michel Carole A. Long Robert E. Sinden Adrian V.S. Hill Simon J. Draper Sumi Biswas 《International journal for parasitology》2013
The mosquito innate immune response is able to clear the majority of Plasmodium parasites. This immune clearance is controlled by a number of regulatory molecules including serine protease inhibitors (serpins). To determine whether such molecules could represent a novel target for a malaria transmission-blocking vaccine, we vaccinated mice with Anopheles gambiae serpin-2. Antibodies against Anopheles gambiae serpin-2 significantly reduced the infection of a heterologous Anopheles species (Anopheles stephensi) by Plasmodium berghei, however this effect was not observed with Plasmodium falciparum. Therefore, this approach of targeting regulatory molecules of the mosquito immune system may represent a novel approach to transmission-blocking malaria vaccines. 相似文献
56.
Desiree?M?Baron Laura?J?Kaushansky Catherine?L?Ward Reddy?Ranjith?K?Sama Ru-Ju?Chian Kristin?J?Boggio Alexandre?J?C?Quaresma Jeffrey?A?Nickerson Daryl?A?BoscoEmail author 《Molecular neurodegeneration》2013,8(1):30
Background
Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis. While the association of mutant-FUS with stress granules is well established, the effect of the mutant protein on stress granules has not been examined. Here we investigated the effect of mutant-FUS on stress granule formation and dynamics under conditions of oxidative stress.Results
We found that expression of mutant-FUS delays the assembly of stress granules. However, once stress granules containing mutant-FUS are formed, they are more dynamic, larger and more abundant compared to stress granules lacking FUS. Once stress is removed, stress granules disassemble more rapidly in cells expressing mutant-FUS. These effects directly correlate with the degree of mutant-FUS cytoplasmic localization, which is induced by mutations in the nuclear localization signal of the protein. We also determine that the RGG domains within FUS play a key role in its association to stress granules. While there has been speculation that arginine methylation within these RGG domains modulates the incorporation of FUS into stress granules, our results demonstrate that this post-translational modification is not involved.Conclusions
Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response.57.
Kristin E Svensson Marianne I Velandia Ann-Sofi T Matthiesen Barbara L Welles-Nyström Ann-Marie E Widström 《International breastfeeding journal》2013,8(1):1-13
Background
Infants with latch-on problems cause stress for parents and staff, often resulting in early termination of breastfeeding. Healthy newborns experiencing skin-to-skin contact at birth are pre-programmed to find the mother’s breast. This study investigates if skin-to-skin contact between mothers with older infants having severe latching on problems would resolve the problem.Methods
Mother-infant pairs with severe latch-on problems, that were not resolved during screening procedures at two maternity hospitals in Stockholm 1998–2004, were randomly assigned to skin-to-skin contact (experimental group) or not (control group) during breastfeeding. Breastfeeding counseling was given to both groups according to a standard model. Participants were unaware of their treatment group. Objectives were to compare treatment groups concerning the proportion of infants regularly latching on, the time from intervention to regular latching on and maternal emotions and pain before and during breastfeeding.Results
On hundred and three mother-infant pairs with severe latch-on problems 1–16 weeks postpartum were randomly assigned and analyzed. There was no significant difference between the groups in the proportion of infants starting regular latching-on (75% experimental group, vs. 86% control group). Experimental group infants, who latched on, had a significantly shorter median time from start of intervention to regular latching on than control infants, 2.0 weeks (Q1 = 1.0, Q3 = 3.7) vs. 4.7 weeks (Q1 = 2.0, Q3 = 8.0), (p-value = 0.020). However, more infants in the experimental group (94%), with a history of “strong reaction” during “hands-on latch intervention”, latched-on within 3 weeks compared to 33% in the control infants (Fisher Exact test p-value = 0.0001). Mothers in the experimental group (n = 53) had a more positive breastfeeding experience according to the Breastfeeding Emotional Scale during the intervention than mothers in the control group (n = 50) (p-value = 0.022).Conclusions
Skin-to-skin contact during breastfeeding seems to immediately enhance maternal positive feelings and shorten the time it takes to resolve severe latch-on problems in the infants who started to latch. An underlying mechanism may be that skin-to-skin contact with the mother during breastfeeding may calm infants with earlier strong reaction to “hands on latch intervention” and relieve the stress which may have blocked the infant’s inborn biological program to find the breast and latch on.Trial registration
Karolinska Clinical Trial Registration number CT20100055 相似文献58.
Soumitra Paul Chowdhury Kristin Dietel Manuela R?ndler Michael Schmid Helmut Junge Rainer Borriss Anton Hartmann Rita Grosch 《PloS one》2013,8(7)
The soil-borne pathogen Rhizoctonia solani is responsible for crop losses on a wide range of important crops worldwide. The lack of effective control strategies and the increasing demand for organically grown food has stimulated research on biological control. The aim of the present study was to evaluate the rhizosphere competence of the commercially available inoculant Bacillus amyloliquefaciens FZB42 on lettuce growth and health together with its impact on the indigenous rhizosphere bacterial community in field and pot experiments. Results of both experiments demonstrated that FZB42 is able to effectively colonize the rhizosphere (7.45 to 6.61 Log 10 CFU g−1 root dry mass) within the growth period of lettuce in the field. The disease severity (DS) of bottom rot on lettuce was significantly reduced from severe symptoms with DS category 5 to slight symptom expression with DS category 3 on average through treatment of young plants with FZB42 before and after planting. The 16S rRNA gene based fingerprinting method terminal restriction fragment length polymorphism (T-RFLP) showed that the treatment with FZB42 did not have a major impact on the indigenous rhizosphere bacterial community. However, the bacterial community showed a clear temporal shift. The results also indicated that the pathogen R. solani AG1-IB affects the rhizosphere microbial community after inoculation. Thus, we revealed that the inoculant FZB42 could establish itself successfully in the rhizosphere without showing any durable effect on the rhizosphere bacterial community. 相似文献
59.
Mary O. Hearst Kristin Biskeborn Mathew Christensen Carrie Cushing 《Obesity (Silver Spring, Md.)》2013,21(1):E26-E32
Objective:
To investigate the prevalence of overweight and obesity among white and American Indian children in a predominantly rural state.Design and Methods:
Using a repeated, cross‐sectional design of school children's height and weight, the study sample included 361,352 measures of children who were 5.0–19.9 years, attending school across 13 academic calendar years. Trained staff measured height, weight, and recorded gender, age, and race. Data were voluntarily reported to the State Department of Health.Results:
American Indian children consistently had higher rates of overweight and obesity compared to white children. Across the years, 16.3% of white students were overweight, whereas 19.3% of American Indian students were overweight. In addition, 14.5% of white children were obese and 25.9% of American Indian children were obese. Examining by rural versus urban schools, prevalence of overweight had been increasing among white male and female students and American Indian female students living in rural areas. Obesity is also increasing among rural white females and male and female American Indian children.Conclusions:
The findings here suggest that although American Indian children are at higher risk, in general, compared to white children, rural populations in general are experiencing increases in childhood overweight and obesity. Targeted rural interventions beginning at an early age are necessary to improve the health of rural children, especially in American Indian communities. 相似文献60.