全文获取类型
收费全文 | 15034篇 |
免费 | 1361篇 |
国内免费 | 312篇 |
出版年
2023年 | 333篇 |
2022年 | 264篇 |
2021年 | 548篇 |
2020年 | 599篇 |
2019年 | 759篇 |
2018年 | 739篇 |
2017年 | 553篇 |
2016年 | 522篇 |
2015年 | 563篇 |
2014年 | 1161篇 |
2013年 | 1593篇 |
2012年 | 815篇 |
2011年 | 910篇 |
2010年 | 680篇 |
2009年 | 606篇 |
2008年 | 661篇 |
2007年 | 663篇 |
2006年 | 536篇 |
2005年 | 444篇 |
2004年 | 375篇 |
2003年 | 301篇 |
2002年 | 229篇 |
2001年 | 160篇 |
2000年 | 120篇 |
1999年 | 132篇 |
1998年 | 151篇 |
1997年 | 127篇 |
1996年 | 114篇 |
1995年 | 108篇 |
1994年 | 127篇 |
1993年 | 122篇 |
1992年 | 109篇 |
1991年 | 102篇 |
1990年 | 89篇 |
1989年 | 61篇 |
1988年 | 73篇 |
1987年 | 60篇 |
1986年 | 64篇 |
1985年 | 179篇 |
1984年 | 179篇 |
1983年 | 111篇 |
1982年 | 129篇 |
1981年 | 107篇 |
1980年 | 91篇 |
1979年 | 75篇 |
1978年 | 66篇 |
1977年 | 45篇 |
1976年 | 31篇 |
1974年 | 41篇 |
1973年 | 32篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
2.
3.
Brain energy disorders and oxidative stress due to chronic hypoperfusion were considered to be the major risk factors in the pathogenesis of dementia. In previous studies, we have demonstrated that acupuncture treatment improved cognitive function of VaD patients and multi-infarct dementia (MID) rats. Acupuncture therapy also increased the activities of glycometabolic enzymes in the brain. But it is not clear whether acupuncture treatment compensates neuronal energy deficit after cerebral ischemic through enhancing the activities of glucose metabolic enzymes and preserving mitochondrial function, and whether acupuncture neuroprotective effect is associated with activations of mitochondrial antioxidative defense system. So, the effect of acupuncture therapy on cognitive function, cerebral blood flow (CBF), mitochondrial respiratory function and oxidative stress in the brain of MID rats was investigated in this study. The results showed that acupuncture treatment significantly improved cognitive abilities and increased regional CBF of MID rats. Acupuncture elevated the activities of total SOD, CuZnSOD and MnSOD, decreased the level of malondialdehyde (MDA) and superoxide anion, regulated the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG) in mitochondria, and raised the level of the respiratory control index (RCI) and P/O ratio and the activities of mitochondrial respiratory enzymes of MID rats. These results indicated that acupuncture treatment improved cognitive function of MID rats; and this improvement might be due to increased CBF, which ameliorated mitochondrial dysfunction induced by ischemia and endogenous oxidative stress system of brain. 相似文献
4.
Alan Agresti Atalanta Ghosh Matilde Bini 《Biometrical journal. Biometrische Zeitschrift》1995,37(7):811-820
Several authors have noted the dependence of kappa measures of inter-rater agreement on the marginal distributions of contingency tables displaying the joint ratings. This paper introduces a smoothed version of kappa computed after raking the table to achieve pre-specified marginal distributions. A comparison of kappa with raked kappa for various margins can indicate the extent of the dependence on the margins, and can indicate how much of the lack of agreement is due to marginal heterogeneity. 相似文献
5.
Major knowledge gaps exist with respect to light-quality regimes in the coastal-zone Strandzha Quercus frainetto (Q.f.) forest region adjoining the southern Bulgarian Black Sea. This paper presents preliminary results that help narrow these
gaps. In conjunction with leaf area index (LAI) field campaigns we undertook measurements with an array of 7 broad-band (ca
40 nm) sensors covering the range 0.40–0.94 μm, plus 1 sensor for UVB (0.297 μm peak) and 1 for photosynthetically active
radiation (PAR). Measurements focused on inside-forest shade conditions at sites 0 to ca 15 km from the Black Sea and at altitudes
up to ca 120 m above sea level. Some of the sites were also studied using a high-resolution spectroradiometer. A sequential
measuring strategy was necessary. This involves potentially large uncertainties, here addressed through estimations of the
variability around the sinusoidal course of daylight. Light-quality regimes were found to be in general support of earlier
studies of deciduous forests. Our data from the broad-band sensors and from the spectroradiometer are mutually supportive.
They indicate a stronger red-shift below Q.f. canopies than below canopies in enclaves dominated by Fagus orientalis and Pinus sylvestris. Transmission in the range 0.50–0.55 μm increases beneath the three types of canopies, most pronounced in the Q.f. case. Analysis of relationships between the inside-forest to open-field irradiance ratio and LAI supports the use of Beer’s
Law. We found a fairly strong relationship between the red (0.66 μm) to far-red (0.73 μm) irradiance ratios (R/FR) and LAI
for the Q.f. forest. In quantitative terms, the result is new for this Q.f. region, and suggests further research to explore whether a two-sensor approach (0.66 and 0.73 μm) might offer possibilities
for further low-cost mapping of the spatio-temporal patterns of R/FR and LAI in Strandzha. Such mapping would assist in further
studies of the region’s forest biogeochemistry and vitality. 相似文献
6.
目的:桥本甲状腺炎是一种自身免疫性甲状腺疾病,且其发病率呈逐年上升趋势,在医疗实践中,HT 被认为是原发性甲状腺
功能减退最常见的原因,同时较易发生甲状腺癌和淋巴瘤。另外,HT 缺乏早期诊断标准,临床上发病隐匿且表现多样,病人多不
易察觉而延误治疗。本文旨在应用microRNA 芯片技术系统筛查HT病变甲状腺组织,以此研究并揭示其HT 的miRNA 表达谱
变化。方法:本研究首先采用microRNA芯片技术,对正常甲状腺组织及桥本甲状腺炎甲状腺组织中microRNA 的表达进行比较,
筛选桥本甲状腺炎中差异性表达的miRNAs。结果:与正常甲状腺相比,在桥本甲状腺炎及其合并甲状腺乳头状癌的一侧桥本甲
状腺炎中分别有39 个和25 个miRNAs 分子发生了差异性表达(P<0.05),比较2 组中共有的miRNAs 发现,miR-142-3p、
miR-338-3p、miR-454、miR-146a、miR-29b-1*、miR-150、miR-223 表达上调,miR-654-5p、miR-601、miR-198、miR-1226* 表达下调
(log2 FC≥ 2,P<0.05);而miR-142-5p 在原发性桥本甲状腺炎中表达显著性升高近8 倍(log2 FC=7.959,P<0.01)。结论:我们通
过microRNA芯片,首次直接系统筛查了桥本甲状腺炎病变组织相关miRNA 表达谱,总体上初步掌握了与正常甲状腺相比,桥
本甲状腺炎及合并甲状腺乳头状癌时其miRNA 表达谱的变化情况,为我们后续的研究提供了方向与基础。 相似文献
7.
Elli Kohen Cahide Kohen Joseph G. Hirschberg Rene Santus Gregory Grabowski Walter Mangel Shimon Gatt Jeffrey Prince 《Cell biochemistry and function》1993,11(3):167-177
Beta-glucosidase activity was evaluated in situ by means of fluorogenic probes in normal human fibroblasts and fibroblasts from homozygous carriers of the Gaucher trait. Probe internalization, targeting to lysosomes and post-cleavage probe retention were the primary concerns. Internalization and targeting were attempted by in situ photosensitized labilization of lysosomal membranes, lysosomotropic detergents and the use of low density lipid (LDL) or the receptor ligand apolipoprotein E (ApoE). Post-cleavage increase of fluorescence with fluoresceinyl (bis) betaglucopyranoside was appreciably above the rather large pre-cleavage emission. In cells incubated overnight with nonylumbelliferylbetaglucoside (UG9) in the presence of bovine serum albumin and in the absence of ApoE, the probe was dealt with as a cytotoxic agent, accumulating in a paranuclear cap, most likely comprising elements of the endoplasmic reticulum (ER) and Golgi apparatus. Targeting of UG9 to lysosomes occurred within 1 to 3 h of preincubation in the presence of ApoE. There was some evidence of specificity, as Gaucher fibroblasts exhibited weaker cleavage of UG9 (by 50 per cent or more) compared to normal fibroblasts, but in the Gaucher cells there was some residual beta-glucosidase activity. Cleavage of UG9 was nearly totally suppressed in Gaucher cells treated with the beta-glucosidase inhibitor, conduritol B epoxide, for 24 h to 7 days. Suppression in the control fibroblasts was evident but to a lesser degree. The in situ method of fluorogenic assay established for beta-glucosidase deficiency, is in principle applicable to enzyme deficiencies in other lysosomal storage diseases, or to evaluate enhanced enzyme activity following gene therapy. 相似文献
8.
Hyun-Jin Kang Tuong Vy Thi Le Kyungmin Kim Jeonghwan Hur Kyeong Kyu Kim Hyun-Ju Park 《Journal of molecular biology》2014
Both G-quadruplex and Z-DNA can be formed in G-rich and repetitive sequences on genome, and their formation and biological functions are controlled by specific proteins. Z-DNA binding proteins, such as human ADAR1, have a highly conserved Z-DNA binding domain having selective affinity to Z-DNA. Here, our study identifies the Z-DNA binding domain of human ADAR1 (hZαADAR1) as a novel G-quadruplex binding protein that recognizes c-myc promoter G-quadruplex formed in NHEIII1 region and represses the gene expression. An electrophoretic migration shift assay shows the binding of hZαADAR1 to the intramolecular c-myc promoter G-quadruplex-forming DNA oligomer. To corroborate the binding of hZαADAR1 to the G-quadruplex, we conducted CD and NMR chemical shift perturbation analyses. CD results indicate that hZαADAR1 stabilizes the parallel-stranded conformation of the c-myc G-quadruplex. The NMR chemical shift perturbation data reveal that the G-quadruplex binding region in hZαADAR1 was almost identical with the Z-DNA binding region. Finally, promoter assay and Western blot analysis show that hZαADAR1 suppresses the c-myc expression promoted by NHEIII1 region containing the G-quadruplex-forming sequence. This finding suggests a novel function of Z-DNA binding protein as a regulator of G-quadruplex-mediated gene expression. 相似文献
9.
《Bioorganic & medicinal chemistry letters》2014,24(18):4523-4528
Osmolytes have been proposed as treatments for neurodegenerative proteinopathies including Alzheimer’s disease. However, for osmolytes to reach the clinic their efficacy must be improved. In this work, copper(I)-catalyzed azide–alkyne cycloaddition chemistry was used to synthesize glycoclusters bearing six copies of trehalose, lactose, galactose or glucose, with the aim of improving the potency of these osmolytes via multivalency. A trehalose glycocluster was found to be superior to monomeric trehalose in its ability to retard the formation of amyloid-beta peptide 40 (Aβ40) fibrils and protect neurons from Aβ40-induced cell death. 相似文献
10.
《Bioorganic & medicinal chemistry letters》2014,24(16):3861-3864
An isopeptide of amyloid β peptide 1–42 (isoAβ42) was considered as a non-aggregative precursor molecule for the highly aggregative Aβ42. It has been applied to biological studies after several pretreatments. Here we report that isoAβ42 is monomeric with a random coil structure at 40 μM without any pretreatment. But we also found that isoAβ42 retains a slight aggregative nature, which is significantly weaker than that of the native Aβ42. 相似文献