全文获取类型
收费全文 | 17176篇 |
免费 | 1418篇 |
国内免费 | 8篇 |
专业分类
18602篇 |
出版年
2024年 | 21篇 |
2023年 | 130篇 |
2022年 | 305篇 |
2021年 | 533篇 |
2020年 | 309篇 |
2019年 | 399篇 |
2018年 | 458篇 |
2017年 | 353篇 |
2016年 | 663篇 |
2015年 | 1073篇 |
2014年 | 1160篇 |
2013年 | 1347篇 |
2012年 | 1627篇 |
2011年 | 1456篇 |
2010年 | 930篇 |
2009年 | 775篇 |
2008年 | 1019篇 |
2007年 | 996篇 |
2006年 | 886篇 |
2005年 | 807篇 |
2004年 | 773篇 |
2003年 | 617篇 |
2002年 | 617篇 |
2001年 | 105篇 |
2000年 | 90篇 |
1999年 | 110篇 |
1998年 | 125篇 |
1997年 | 97篇 |
1996年 | 90篇 |
1995年 | 65篇 |
1994年 | 60篇 |
1993年 | 49篇 |
1992年 | 48篇 |
1991年 | 38篇 |
1990年 | 37篇 |
1989年 | 48篇 |
1988年 | 38篇 |
1987年 | 24篇 |
1986年 | 20篇 |
1985年 | 28篇 |
1984年 | 30篇 |
1983年 | 22篇 |
1982年 | 19篇 |
1981年 | 18篇 |
1980年 | 21篇 |
1979年 | 19篇 |
1978年 | 13篇 |
1976年 | 17篇 |
1974年 | 13篇 |
1968年 | 10篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Alicia M. Waters Laura L. Stafman Evan F. Garner Smitha Mruthyunjayappa Jerry E. Stewart Gregory K. Friedman Jennifer M. Coleman James M. Markert G. Yancey Gillespie Elizabeth A. Beierle 《Translational oncology》2016,9(5):419-430
Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these aggressive malignancies. Genetically engineered oncolytic viruses, such as herpes simplex virus-1 (HSV), are currently being explored as treatments for pediatric tumors. M002, an oncolytic HSV, has both copies of the γ134.5 gene deleted, enabling replication in tumor cells but thwarting infection of normal, postmitotic cells. We hypothesized that M002 would infect human RMS tumor cells and lead to decreased tumor cell survival in vitro and impede tumor growth in vivo. In the current study, we demonstrated that M002 could infect, replicate in, and decrease cell survival in both embryonal (ERMS) and alveolar rhabdomyosarcoma (ARMS) cells. Additionally, M002 reduced xenograft tumor growth and increased animal survival in both ARMS and ERMS. Most importantly, we showed for the first time that repeated dosing of oncolytic virus coupled with low-dose radiation provided improved tumor response in RMS. These findings provide support for the clinical investigation of oncolytic HSV in pediatric RMS. 相似文献
992.
993.
Stomatal acclimation to vapour pressure deficit doubles transpiration of small tree seedlings with warming 总被引:1,自引:0,他引:1 下载免费PDF全文
Renée M. Marchin Alice A. Broadhead Laura E. Bostic Robert R. Dunn William A. Hoffmann 《Plant, cell & environment》2016,39(10):2221-2234
Future climate change is expected to increase temperature (T) and atmospheric vapour pressure deficit (VPD) in many regions, but the effect of persistent warming on plant stomatal behaviour is highly uncertain. We investigated the effect of experimental warming of 1.9–5.1 °C and increased VPD of 0.5–1.3 kPa on transpiration and stomatal conductance (gs) of tree seedlings in the temperate forest understory (Duke Forest, North Carolina, USA). We observed peaked responses of transpiration to VPD in all seedlings, and the optimum VPD for transpiration (Dopt) shifted proportionally with increasing chamber VPD. Warming increased mean water use of Carya by 140% and Quercus by 150%, but had no significant effect on water use of Acer. Increased water use of ring‐porous species was attributed to (1) higher air T and (2) stomatal acclimation to VPD resulting in higher gs and more sensitive stomata, and thereby less efficient water use. Stomatal acclimation maintained homeostasis of leaf T and carbon gain despite increased VPD, revealing that short‐term stomatal responses to VPD may not be representative of long‐term exposure. Acclimation responses differ from expectations of decreasing gs with increasing VPD and may necessitate revision of current models based on this assumption. 相似文献
994.
Nhu H. Nguyen Laura J. Williams John B. Vincent Artur Stefanski Jeannine Cavender‐Bares Christian Messier Alain Paquette Dominique Gravel Peter B. Reich Peter G. Kennedy 《Molecular ecology》2016,25(16):4032-4046
Exploring the link between above‐ and belowground biodiversity has been a major theme of recent ecological research, due in large part to the increasingly well‐recognized role that soil microorganisms play in driving plant community processes. In this study, we utilized a field‐based tree experiment in Minnesota, USA, to assess the effect of changes in plant species richness and phylogenetic diversity on the richness and composition of both ectomycorrhizal and saprotrophic fungal communities. We found that ectomycorrhizal fungal species richness was significantly positively influenced by increasing plant phylogenetic diversity, while saprotrophic fungal species richness was significantly affected by plant leaf nitrogen content, specific root length and standing biomass. The increasing ectomycorrhizal fungal richness associated with increasing plant phylogenetic diversity was driven by the combined presence of ectomycorrhizal fungal specialists in plots with both gymnosperm and angiosperm hosts. Although the species composition of both the ectomycorrhizal and saprotrophic fungal communities changed significantly in response to changes in plant species composition, the effect was much greater for ectomycorrhizal fungi. In addition, ectomycorrhizal but not saprotrophic fungal species composition was significantly influenced by both plant phylum (angiosperm, gymnosperm, both) and origin (Europe, America, both). The phylum effect was caused by differences in ectomycorrhizal fungal community composition, while the origin effect was attributable to differences in community heterogeneity. Taken together, this study emphasizes that plant‐associated effects on soil fungal communities are largely guild‐specific and provides a mechanistic basis for the positive link between plant phylogenetic diversity and ectomycorrhizal fungal richness. 相似文献
995.
996.
Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV. 相似文献
997.
Snow JB Gonzalez Bosc LV Kanagy NL Walker BR Resta TC 《American journal of physiology. Lung cellular and molecular physiology》2011,301(5):L745-L754
Intermittent hypoxia (IH) resulting from sleep apnea causes both systemic and pulmonary hypertension. Enhanced endothelin-1 (ET-1)-induced vasoconstrictor reactivity is thought to play a central role in the systemic hypertensive response to IH. However, whether IH similarly increases pulmonary vasoreactivity and the signaling mechanisms involved are unknown. The objective of the present study was to test the hypothesis that IH augments ET-1-induced pulmonary vasoconstrictor reactivity through a PKCβ-dependent signaling pathway. Responses to ET-1 were assessed in endothelium-disrupted, pressurized pulmonary arteries (~150 μm inner diameter) from eucapnic-IH [(E-IH) 3 min cycles, 5% O(2)-5% CO(2)/air flush, 7 h/day; 4 wk] and sham (air-cycled) rats. Arteries were loaded with fura-2 AM to monitor vascular smooth muscle (VSM) intracellular Ca(2+) concentration ([Ca(2+)](i)). E-IH increased vasoconstrictor reactivity without altering Ca(2+) responses, suggestive of myofilament Ca(2+) sensitization. Consistent with our hypothesis, inhibitors of both PKCα/β (myr-PKC) and PKCβ (LY-333-531) selectively decreased vasoconstriction to ET-1 in arteries from E-IH rats and normalized responses between groups, whereas Rho kinase (fasudil) and PKCδ (rottlerin) inhibition were without effect. Although E-IH did not alter arterial PKCα/β mRNA or protein expression, E-IH increased basal PKCβI/II membrane localization and caused ET-1-induced translocation of these isoforms away from the membrane fraction. We conclude that E-IH augments pulmonary vasoconstrictor reactivity to ET-1 through a novel PKCβ-dependent mechanism that is independent of altered PKC expression. These findings provide new insights into signaling mechanisms that contribute to vasoconstriction in the hypertensive pulmonary circulation. 相似文献
998.
Regulation of protein transport within the early secretory pathway is a relatively unexplored area. Here, we propose a new player in the control of protein transport from the endoplasmic reticulum (ER) to the Golgi. Akt is an important signaling kinase whose functioning is perturbed in diseases such as cancer and diabetes. We discovered that Akt phosphorylates Sec24, an essential coat protein II (COPII) component involved in mediating cargo selection for ER-to-Golgi trafficking. We discuss how this finding may provide new insights into the regulation of protein transport. 相似文献
999.
Vaites LP Lee EK Lian Z Barbash O Roy D Wasik M Klein-Szanto AJ Rustgi AK Diehl JA 《Molecular and cellular biology》2011,31(22):4513-4523
Skp1-Cul1-F-box (SCF) E3 ubiquitin ligase complexes modulate the accumulation of key cell cycle regulatory proteins. Following the G(1)/S transition, SCF(Fbx4) targets cyclin D1 for proteasomal degradation, a critical event necessary for DNA replication fidelity. Deregulated cyclin D1 drives tumorigenesis, and inactivating mutations in Fbx4 have been identified in human cancer, suggesting that Fbx4 may function as a tumor suppressor. Fbx4(+/-) and Fbx4(-/-) mice succumb to multiple tumor phenotypes, including lymphomas, histiocytic sarcomas and, less frequently, mammary and hepatocellular carcinomas. Tumors and premalignant tissue from Fbx4(+/-) and Fbx4(-/-) mice exhibit elevated cyclin D1, an observation consistent with cyclin D1 as a target of Fbx4. Molecular dissection of the Fbx4 regulatory network in murine embryonic fibroblasts (MEFs) revealed that loss of Fbx4 results in cyclin D1 stabilization and nuclear accumulation throughout cell division. Increased proliferation in early passage primary MEFs is antagonized by DNA damage checkpoint activation, consistent with nuclear cyclin D1-driven genomic instability. Furthermore, Fbx4(-/-) MEFs exhibited increased susceptibility to Ras-dependent transformation in vitro, analogous to tumorigenesis observed in mice. Collectively, these data reveal a requisite role for the SCF(Fbx4) E3 ubiquitin ligase in regulating cyclin D1 accumulation, consistent with tumor suppressive function in vivo. 相似文献
1000.
The effect of inbreeding on genetic diversity is expected to decrease plant defences or vigour-related traits that, in turn,
can modify the pattern of attack by herbivores. The selective damage caused by herbivores can produce variable fitness costs
between inbred and outcrossed progenies influencing the evolution of a species’ plant mating system. By exposing inbred and
outcrossed plants to natural conditions of seed predation, we assessed whether inbreeding increases weevil incidence and infestation,
and how weevil seed predation affects the fitness of inbred and outcrossed progeny. To test if inbreeding affected the host’s
plant quality, we weighed the biomass of weevils developed in inbred and outcrossed progenies. An additional experiment was
carried out to examine whether weevils preferentially attack vigorous plants regardless from the level of inbreeding. The
average value of leaf size was 21% larger in outcrossed plants than in inbred plants. Likewise, weevil incidence and infestation
were 13 and 40%, respectively, higher on outcrossed plants relative to their inbred counterparts. However, the relative impact
of seed predation was significantly lower in outcrossed progeny than in inbred progeny. In contrast, inbreeding did not alter
host plant quality and weevils developed in inbred and outcrossed plants had a similar biomass. Variations in fruit number
were consistently associated with the infestation level in both experiments, whereas leaf size only predicted the number of
weevils in one experiment, suggesting that fruit number is the most influential vigour-related characteristic of a weevil
attack. These findings indicate that the costs of inbreeding of the interaction D. stramonium-T. soror were higher for inbred plants than for outcrossed plants. The interaction between seed predation and inbreeding depression
could prevent the fixation of selfing as a unique reproductive strategy in D. stramonium. 相似文献