全文获取类型
收费全文 | 3608篇 |
免费 | 420篇 |
国内免费 | 2篇 |
专业分类
4030篇 |
出版年
2023年 | 17篇 |
2022年 | 44篇 |
2021年 | 78篇 |
2020年 | 49篇 |
2019年 | 55篇 |
2018年 | 59篇 |
2017年 | 54篇 |
2016年 | 99篇 |
2015年 | 194篇 |
2014年 | 221篇 |
2013年 | 218篇 |
2012年 | 335篇 |
2011年 | 326篇 |
2010年 | 204篇 |
2009年 | 165篇 |
2008年 | 247篇 |
2007年 | 193篇 |
2006年 | 189篇 |
2005年 | 204篇 |
2004年 | 172篇 |
2003年 | 164篇 |
2002年 | 133篇 |
2001年 | 62篇 |
2000年 | 38篇 |
1999年 | 53篇 |
1998年 | 44篇 |
1997年 | 24篇 |
1996年 | 26篇 |
1995年 | 26篇 |
1994年 | 28篇 |
1993年 | 19篇 |
1992年 | 19篇 |
1991年 | 26篇 |
1990年 | 26篇 |
1989年 | 27篇 |
1988年 | 17篇 |
1987年 | 21篇 |
1986年 | 17篇 |
1985年 | 20篇 |
1984年 | 7篇 |
1983年 | 16篇 |
1982年 | 6篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 9篇 |
1977年 | 5篇 |
1968年 | 10篇 |
1967年 | 8篇 |
1959年 | 3篇 |
排序方式: 共有4030条查询结果,搜索用时 15 毫秒
71.
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
72.
Witold Kot Karin Hammer Horst Neve Finn K. Vogensen 《Applied and environmental microbiology》2013,79(10):3311-3314
Two phages, P793 and ΦLN04, sharing 80.1% nucleotide sequence identity but having different strains of Leuconostoc pseudomesenteroides as hosts, were selected for identification of the host determinant gene. Construction of chimeric phages leading to the expected switch in host range identified the host determinant genes as ORF21P793/ORF23ΦLN04. The genes are located in the tail structural module and have low sequence similarity at the distal end. 相似文献
73.
74.
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
75.
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
76.
Ingo V. Hartung Marion Hitchcock Florian Pühler Roland Neuhaus Arne Scholz Stefanie Hammer Kirstin Petersen Gerhard Siemeister Dominic Brittain Roman C. Hillig 《Bioorganic & medicinal chemistry letters》2013,23(8):2384-2390
Using PD325901 as a starting point for identifying novel allosteric MEK inhibitors with high cell potency and long-lasting target inhibition in vivo, truncation of its hydroxamic ester headgroup was combined with incorporation of alkyl and aryl ethers at the neighboring ring position. Whereas alkoxy side chains did not yield sufficient levels of cell potency, specifically substituted aryloxy groups allowed for high enzymatic and cellular potencies. Sulfamide 28 was identified as a highly potent MEK inhibitor with nanomolar cell potency against B-RAF (V600E) as well as Ras-mutated cell lines, high metabolic stability and resulting long half-lives. It was efficacious against B-RAF as well as K-Ras driven xenograft models and showed—despite being orally bioavailable and not a P-glycoprotein substrate—much lower brain/plasma exposure ratios than PD325901. 相似文献
77.
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78.
Geoffrey Guest Francesco Cherubini Anders Hammer Strømman 《Global Change Biology Bioenergy》2013,5(4):459-466
Bioenergy makes up a significant portion of the global primary energy pie, and its production from modernized technology is foreseen to substantially increase. The climate neutrality of biogenic CO2 emissions from bioenergy grown from sustainably managed biomass resource pools has recently been questioned. The temporary change caused in atmospheric CO2 concentration from biogenic carbon fluxes was found to be largely dependent on the length of biomass rotation period. In this work, we also show the importance of accounting for the unutilized biomass that is left to decompose in the resource pool and how the characterization factor for the climate impact of biogenic CO2 emissions changes whether residues are removed for bioenergy or not. With the case of Norwegian Spruce biomass grown in Norway, we found that significantly more biogenic CO2 emissions should be accounted towards contributing to global warming potential when residues are left in the forest. For a 100‐year time horizon, the global warming potential bio factors suggest that between 44 and 62% of carbon‐flux, neutral biogenic CO2 emissions at the energy conversion plant should be attributed to causing equivalent climate change potential as fossil‐based CO2 emissions. For a given forest residue extraction scenario, the same factor should be applied to the combustion of any combination of stem and forest residues. Life cycle analysis practitioners should take these impacts into account and similar region/species specific factors should be developed. 相似文献
79.
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
80.
Mary O. Hearst Kristin Biskeborn Mathew Christensen Carrie Cushing 《Obesity (Silver Spring, Md.)》2013,21(1):E26-E32