全文获取类型
收费全文 | 7126篇 |
免费 | 975篇 |
出版年
2021年 | 84篇 |
2019年 | 70篇 |
2017年 | 73篇 |
2016年 | 99篇 |
2015年 | 183篇 |
2014年 | 213篇 |
2013年 | 256篇 |
2012年 | 321篇 |
2011年 | 323篇 |
2010年 | 222篇 |
2009年 | 197篇 |
2008年 | 302篇 |
2007年 | 287篇 |
2006年 | 274篇 |
2005年 | 224篇 |
2004年 | 221篇 |
2003年 | 199篇 |
2002年 | 208篇 |
2001年 | 230篇 |
2000年 | 188篇 |
1999年 | 154篇 |
1998年 | 88篇 |
1997年 | 108篇 |
1996年 | 95篇 |
1995年 | 84篇 |
1994年 | 73篇 |
1993年 | 88篇 |
1992年 | 139篇 |
1991年 | 127篇 |
1990年 | 137篇 |
1989年 | 152篇 |
1988年 | 129篇 |
1987年 | 132篇 |
1986年 | 101篇 |
1985年 | 150篇 |
1984年 | 136篇 |
1983年 | 99篇 |
1982年 | 121篇 |
1981年 | 150篇 |
1980年 | 119篇 |
1979年 | 107篇 |
1978年 | 85篇 |
1977年 | 88篇 |
1976年 | 94篇 |
1975年 | 73篇 |
1974年 | 87篇 |
1973年 | 68篇 |
1972年 | 68篇 |
1971年 | 71篇 |
1969年 | 76篇 |
排序方式: 共有8101条查询结果,搜索用时 15 毫秒
991.
992.
Cooper DL Martin SG Robinson JI Mackie SL Charles CJ Nam J;YEAR Consortium Isaacs JD Emery P Morgan AW 《PloS one》2012,7(1):e28918
Objective
The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC). We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA), associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy.Methods
FcγRIIIa/CD16 expression on CD14low and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease). Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG) activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined.Results
Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002) with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001). The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003) and was significantly increased in EULAR non-responders compared to moderate (p = 0.01) or good responders (p = 0.003). FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers.Conclusion
Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy. 相似文献993.
Although rarely acknowledged, our understanding of how competition is modulated by environmental drivers is severely hampered by our dependence on indirect measurements of outcomes, rather than the process of competition. To overcome this, we made direct measurements of plant competition for soil nitrogen (N). Using isotope pool-dilution, we examined the interactive effects of soil resource limitation and climatic severity between two common grassland species. Pool-dilution estimates the uptake of total N over a defined time period, rather than simply the uptake of 15N label, as used in most other tracer experiments. Competitive uptake of N was determined by its available form (NO3
− or NH4
+). Soil N availability had a greater effect than the climatic conditions (location) under which plants grew. The results did not entirely support either of the main current theories relating the role of competition to environmental conditions. We found no evidence for Tilman''s theory that competition for soil nutrients is stronger at low, compared with high nutrient levels and partial support for Grime''s theory that competition for soil nutrients is greater under potentially more productive conditions. These results provide novel insights by demonstrating the dynamic nature of plant resource competition. 相似文献
994.
995.
996.
Dana R. Warren Jason M. Robinson Daniel C. Josephson Daniel R. Sheldon Clifford E. Kraft 《Global Change Biology》2012,18(6):1804-1811
Redd (nest) surveys for resident brook trout (Salvelinus fontinalis) were conducted annually in a mountain lake in northern New York for 11 years with multiple surveys conducted during the spawning season in eight of those years. Repeated surveys throughout the spawning season allowed us to fit an individually based parametric model and estimate the day of year on which spawning was initiated, reached its midpoint, and ended during each year. Spawning phenology was then assessed relative to (1) mean of maximum daily air temperature and (2) mean of maximum daily water temperature at the lake bottom during summer in each year using a linear model. Elevated temperatures in summer were correlated with a delay in spawning and a reduction in the total number of redds constructed. Increasing the summer mean of maximum daily air temperatures by 1 °C delayed spawning by approximately 1 week and decreased the total number of redds constructed by nearly 65. Lake spawning brook trout select redd sites based on the presence of discharging groundwater that is relatively constant in temperature within and across years, leading to relatively consistent egg incubation times. Therefore, delayed spawning is likely to delay fry emergence, which could influence emergence synchrony with prey items. This work highlights non‐lethal and sub‐lethal effects of elevated summer temperatures on native resident salmonids in aquatic environments with limited thermal refugia. 相似文献
997.
998.
Robinson AB Johnson KD Bennion BG Reynolds PR 《American journal of physiology. Lung cellular and molecular physiology》2012,302(11):L1192-L1199
Receptors for advanced glycation end-products (RAGE) are multiligand cell surface receptors of the immunoglobin family expressed by epithelium and macrophages, and expression increases following exposure to cigarette smoke extract (CSE). The present study sought to characterize the proinflammatory contributions of RAGE expressed by alveolar macrophages (AMs) following CSE exposure. Acute exposure of mice to CSE via nasal instillation revealed diminished bronchoalveolar lavage (BAL) cellularity and fewer AMs in RAGE knockout (KO) mice compared with controls. Primary AMs were obtained from BAL, exposed to CSE in vitro, and analyzed. CSE significantly increased RAGE expression by wild-type AMs. Employing ELISAs, wild-type AMs exposed to CSE had increased levels of active Ras, a small GTPase that perpetuates proinflammatory signaling. Conversely, RAGE KO AMs had less Ras activation compared with wild-type AMs after exposure to CSE. In RAGE KO AMs, assessment of p38 MAPK and NF-κB, important intracellular signaling intermediates induced during an inflammatory response, revealed that CSE-induced inflammation may occur in part via RAGE signaling. Lastly, quantitative RT-PCR revealed that the expression of proinflammatory cytokines including TNF-α and IL-1β were detectably decreased in RAGE KO AMs exposed to CSE compared with CSE-exposed wild-type AMs. These results reveal that primary AMs orchestrate CSE-induced inflammation, at least in part, via RAGE-mediated mechanisms. 相似文献
999.
Johnson JA Hemnes AR Perrien DS Schuster M Robinson LJ Gladson S Loibner H Bai S Blackwell TR Tada Y Harral JW Talati M Lane KB Fagan KA West J 《American journal of physiology. Lung cellular and molecular physiology》2012,302(5):L474-L484
The heritable form of pulmonary arterial hypertension (PAH) is typically caused by a mutation in bone morphogenic protein receptor type 2 (BMPR2), and mice expressing Bmpr2 mutations develop PAH with features similar to human disease. BMPR2 is known to interact with the cytoskeleton, and human array studies in PAH patients confirm alterations in cytoskeletal pathways. The goal of this study was to evaluate cytoskeletal defects in BMPR2-associated PAH. Expression arrays on our Bmpr2 mutant mouse lungs revealed cytoskeletal defects as a prominent molecular consequence of universal expression of a Bmpr2 mutation (Rosa26-Bmpr2(R899X)). Pulmonary microvascular endothelial cells cultured from these mice have histological and functional cytoskeletal defects. Stable transfection of different BMPR2 mutations into pulmonary microvascular endothelial cells revealed that cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. Rac1 defects are corrected in cell culture and in vivo through administration of exogenous recombinant human angiotensin-converting enzyme 2 (rhACE2). rhACE2 reverses 77% of gene expression changes in Rosa26-Bmpr2(R899X) transgenic mice, in particular, correcting defects in cytoskeletal function. Administration of rhACE2 to Rosa26-Bmpr2(R899X) mice with established PAH normalizes pulmonary pressures. Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease. 相似文献
1000.
Reis GF Yang G Szpankowski L Weaver C Shah SB Robinson JT Hays TS Danuser G Goldstein LS 《Molecular biology of the cell》2012,23(9):1700-1714
Bidirectional axonal transport driven by kinesin and dynein along microtubules is critical to neuronal viability and function. To evaluate axonal transport mechanisms, we developed a high-resolution imaging system to track the movement of amyloid precursor protein (APP) vesicles in Drosophila segmental nerve axons. Computational analyses of a large number of moving vesicles in defined genetic backgrounds with partial reduction or overexpression of motor proteins enabled us to test with high precision existing and new models of motor activity and coordination in vivo. We discovered several previously unknown features of vesicle movement, including a surprising dependence of anterograde APP vesicle movement velocity on the amount of kinesin-1. This finding is largely incompatible with the biophysical properties of kinesin-1 derived from in vitro analyses. Our data also suggest kinesin-1 and cytoplasmic dynein motors assemble in stable mixtures on APP vesicles and their direction and velocity are controlled at least in part by dynein intermediate chain. 相似文献