全文获取类型
收费全文 | 6202篇 |
免费 | 616篇 |
国内免费 | 9篇 |
专业分类
6827篇 |
出版年
2023年 | 25篇 |
2022年 | 58篇 |
2021年 | 94篇 |
2020年 | 79篇 |
2019年 | 72篇 |
2018年 | 94篇 |
2017年 | 80篇 |
2016年 | 114篇 |
2015年 | 211篇 |
2014年 | 241篇 |
2013年 | 295篇 |
2012年 | 367篇 |
2011年 | 407篇 |
2010年 | 264篇 |
2009年 | 210篇 |
2008年 | 320篇 |
2007年 | 356篇 |
2006年 | 340篇 |
2005年 | 339篇 |
2004年 | 291篇 |
2003年 | 269篇 |
2002年 | 295篇 |
2001年 | 75篇 |
2000年 | 82篇 |
1999年 | 97篇 |
1998年 | 86篇 |
1997年 | 57篇 |
1996年 | 48篇 |
1995年 | 60篇 |
1994年 | 49篇 |
1993年 | 45篇 |
1992年 | 54篇 |
1991年 | 59篇 |
1990年 | 59篇 |
1989年 | 53篇 |
1988年 | 46篇 |
1987年 | 36篇 |
1986年 | 36篇 |
1985年 | 46篇 |
1984年 | 35篇 |
1983年 | 43篇 |
1982年 | 46篇 |
1981年 | 52篇 |
1980年 | 51篇 |
1979年 | 40篇 |
1978年 | 32篇 |
1976年 | 41篇 |
1975年 | 37篇 |
1974年 | 25篇 |
1973年 | 27篇 |
排序方式: 共有6827条查询结果,搜索用时 15 毫秒
1.
2.
Electrical stimulation of the nervous system for therapeutic purposes, such as deep brain stimulation in the treatment of Parkinson’s disease, has been used for decades. Recently, increased attention has focused on using microstimulation to restore functions as diverse as somatosensation and memory. However, how microstimulation changes the neural substrate is still not fully understood. Microstimulation may cause cortical changes that could either compete with or complement natural neural processes, and could result in neuroplastic changes rendering the region dysfunctional or even epileptic. As part of our efforts to produce neuroprosthetic devices and to further study the effects of microstimulation on the cortex, we stimulated and recorded from microelectrode arrays in the hand area of the primary somatosensory cortex (area 1) in two awake macaque monkeys. We applied a simple neuroprosthetic microstimulation protocol to a pair of electrodes in the area 1 array, using either random pulses or pulses time-locked to the recorded spiking activity of a reference neuron. This setup was replicated using a computer model of the thalamocortical system, which consisted of 1980 spiking neurons distributed among six cortical layers and two thalamic nuclei. Experimentally, we found that spike-triggered microstimulation induced cortical plasticity, as shown by increased unit-pair mutual information, while random microstimulation did not. In addition, there was an increased response to touch following spike-triggered microstimulation, along with decreased neural variability. The computer model successfully reproduced both qualitative and quantitative aspects of the experimental findings. The physiological findings of this study suggest that even simple microstimulation protocols can be used to increase somatosensory information flow. 相似文献
3.
R T Francis R R Becker 《Comparative biochemistry and physiology. A, Comparative physiology》1984,79(1):109-113
The capability of Taricha granulosa to conserve hemoglobin upon in vivo hemolysis has been investigated. 59Fe incorporation into Taricha hemoglobin was similar in rate to mammals and birds. Phenylhydrazine-induced hemolysis resulted in comparatively low levels of 59Fe and no discernible amounts of hemoglobin excreted after 10 days. The addition of 59Fe Hb to Taricha circulation resulted in relatively low levels of 59Fe excretion and significant amounts of 59Fe incorporation into new hemoglobin within 10 days. 相似文献
4.
Young J. Oh Jonathan W. Francis George J. Markelonis Tae H. Oh 《Journal of neurochemistry》1992,58(6):2131-2138
Peripheral-type benzodiazepine binding sites (PTBBS) are markedly increased in the injured CNS. Astrocytes appear to be the primary cell type which express increased PTBBS. Because certain cytokines within the injured CNS are potent mitogens for astrocytes, we examined the effects of two such cytokines, interleukin (IL)-1 beta and tumor necrosis factor (TNF), on PTBBS in cultured astrocytes using [3H]Ro 5-4864 as the specific ligand. Purified cultures of either polygonal or process-bearing astrocytes were prepared from neonatal rat cerebral hemispheres. At a concentration of 1.8 nM, specific binding of the radioactive ligand to polygonal astrocytes reached equilibrium within 60 min and was half-maximal by 5-10 min. By contrast, specific binding to process-bearing astrocytes barely exceeded background levels. IL-1 and TNF increased PTBBS within polygonal astrocytes in both dose- and time-dependent manners. At 10-50 ng/ml, IL-1 beta and TNF-alpha elevated [3H]Ro 5-4864 binding in polygonal astrocyte cultures 65 and 87%, respectively, above the level in control cultures. However, no changes in PTBBS were seen within polygonal astrocytes after IL-2 treatment. Scatchard analysis of saturation binding experiments suggested that the increase in PTBBS promoted by TNF was due to an increased number of binding sites present in polygonal astrocytes and not due to an increase in receptor affinity. Binding data suggested that PTBBS within cultures of process-bearing astrocytes were virtually absent irrespective of the treatment. These in vitro data suggest that certain cytokines found in the injured brain may be involved in up-regulating PTBBS within a particular subtype of astrocyte. 相似文献
5.
6.
Cutting edge: precursor frequency affects the helper dependence of cytotoxic T cells. 总被引:3,自引:0,他引:3
Justine D Mintern Gayle M Davey Gabrielle T Belz Francis R Carbone William R Heath 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(3):977-980
Generation of CTL immunity often depends on the availability of CD4 T cell help. In this report, we show that CTL responses induced by cross-priming can be converted from CD4-dependent to CD4-independent by increasing the frequency of CTL precursors. In the absence of CD4 T cells, high numbers of CTL precursors were able to expand in number and become effector CTL. The ability of high frequencies of CD8 T cells to override help was not due to their ability to signal CD40 via expression of CD154. These findings suggest that when precursor frequencies are high, priming of CD8 T cell responses may not require CD4 T cell help. 相似文献
7.
Francis G Blankenberg Zoia Levashova Susanta K Sarkar John Pizzonia Marina V Backer Joseph M Backer 《Translational oncology》2010,3(1):56-64
Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) drive angiogenesis, and several VEGFR inhibitors are already approved for use as single agents or in combination with chemotherapy. Although there is a clear benefit with these drugs in a variety of tumors, the clinical response varies markedly among individuals. Therefore, there is a need for an efficient method to identify patients who are likely to respond to antiangiogenic therapy and to monitor its effects over time. We have recently developed a molecular imaging tracer for imaging VEGFRs known as scVEGF/99mTc; an engineered single-chain (sc) form of VEGF radiolabeled with technetium Tc 99m (99mTc). After intravenous injection, scVEGF/99mTc preferentially binds to and is internalized by VEGFRs expressed within tumor vasculature, providing information on prevalence of functionally active receptors. We now report that VEGFR imaging readily detects the effects of pazopanib, a small-molecule tyrosine kinase inhibitor under clinical development, which selectively targets VEGFR, PDGFR, and c-Kit in mice with HT29 tumor xenografts. Immunohistochemical analysis confirmed that the changes in VEGFR imaging reflect a dramatic pazopanib-induced decrease in the number of VEGFR-2+/CD31+ endothelial cells (ECs) within the tumor vasculature followed by a relative increase in the number of ECs at the tumor edges. We suggest that VEGFR imaging can be used for the identification of patients that are responding to VEGFR-targeted therapies and for guidance in rational design, dosing, and schedules for combination regimens of antiangiogenic treatment. 相似文献
8.
Francis G. Spinale Rupak Mukherjee Juozas A. Zavadzkas Christine N. Koval Shenikqua Bouges Robert E. Stroud Lawrence W. Dobrucki Albert J. Sinusas 《The Journal of biological chemistry》2010,285(39):30316-30327
The membrane type-1 matrix metalloproteinase (MT1-MMP) is a unique member of the MMP family, but induction patterns and consequences of MT1-MMP overexpression (MT1-MMPexp), in a left ventricular (LV) remodeling process such as myocardial infarction (MI), have not been explored. MT1-MMP promoter activity (murine luciferase reporter) increased 20-fold at 3 days and 50-fold at 14 days post-MI. MI was then induced in mice with cardiac restricted MT1-MMPexp (n = 58) and wild type (WT, n = 60). Post-MI survival was reduced (67% versus 46%, p < 0.05), and LV ejection fraction was lower in the post-MI MT1-MMPexp mice compared with WT (41 ± 2 versus 32 ± 2%,p < 0.05). In the post-MI MT1-MMPexp mice, LV myocardial MMP activity, as assessed by radiotracer uptake, and MT1-MMP-specific proteolytic activity using a specific fluorogenic assay were both increased by 2-fold. LV collagen content was increased by nearly 2-fold in the post-MI MT1-MMPexp compared with WT. Using a validated fluorogenic construct, it was discovered that MT1-MMP proteolytically processed the pro-fibrotic molecule, latency-associated transforming growth factor-1 binding protein (LTBP-1), and MT1-MMP-specific LTBP-1 proteolytic activity was increased by 4-fold in the post-MI MT1-MMPexp group. Early and persistent MT1-MMP promoter activity occurred post-MI, and increased myocardial MT1-MMP levels resulted in poor survival, worsening of LV function, and significant fibrosis. A molecular mechanism for the adverse LV matrix remodeling with MT1-MMP induction is increased processing of pro-fibrotic signaling molecules. Thus, a proteolytically diverse portfolio exists for MT1-MMP within the myocardium and likely plays a mechanistic role in adverse LV remodeling. 相似文献
9.
10.
Francis R. Trainor 《Journal of phycology》1966,2(2):85-89
Four strains of Scenedesmus parisiensis Chodat were studied in xenic and axenic culture in 3 media as well as in cultures incubated in sterile vessels in nature. Organized coenobia are usually produced but these may have merely short spines, spines and serrate edges, or lack wall ornamentation. Because the serrate edge is either not formed or cannot be readily detected in most cases, it is not a satisfactory morphological feature for delimiting this species. In laboratory studies it is noted that S. parisiensis might be confused with S. denticulatus rather than S. brasilien-sis. Inasmuch as both xenic and axenic cultures of the -f strains produced similar results, S. parisiensis can be readily characterized. 相似文献