全文获取类型
收费全文 | 29151篇 |
免费 | 2125篇 |
国内免费 | 1609篇 |
专业分类
32885篇 |
出版年
2024年 | 64篇 |
2023年 | 345篇 |
2022年 | 831篇 |
2021年 | 1406篇 |
2020年 | 961篇 |
2019年 | 1188篇 |
2018年 | 1166篇 |
2017年 | 828篇 |
2016年 | 1228篇 |
2015年 | 1896篇 |
2014年 | 2126篇 |
2013年 | 2287篇 |
2012年 | 2612篇 |
2011年 | 2290篇 |
2010年 | 1452篇 |
2009年 | 1235篇 |
2008年 | 1515篇 |
2007年 | 1332篇 |
2006年 | 1168篇 |
2005年 | 980篇 |
2004年 | 790篇 |
2003年 | 695篇 |
2002年 | 533篇 |
2001年 | 479篇 |
2000年 | 379篇 |
1999年 | 411篇 |
1998年 | 243篇 |
1997年 | 265篇 |
1996年 | 252篇 |
1995年 | 214篇 |
1994年 | 217篇 |
1993年 | 150篇 |
1992年 | 216篇 |
1991年 | 184篇 |
1990年 | 130篇 |
1989年 | 106篇 |
1988年 | 79篇 |
1987年 | 108篇 |
1986年 | 82篇 |
1985年 | 69篇 |
1984年 | 52篇 |
1983年 | 36篇 |
1982年 | 36篇 |
1981年 | 26篇 |
1980年 | 21篇 |
1979年 | 25篇 |
1978年 | 17篇 |
1975年 | 21篇 |
1974年 | 18篇 |
1972年 | 17篇 |
排序方式: 共有10000条查询结果,搜索用时 17 毫秒
261.
Rui Cheng Xiaoman Zheng Yingmei Wang Xing Ma Xin Liu Wenjun Xu Mengyun Wang Yuanpeng Gao Xupeng Xing Chuan Zhou Hongzheng Sun Zekun Guo Fusheng Quan Jun Liu Song Hua Yongsheng Wang Yong Zhang Xu Liu 《中国科学:生命科学英文版》2022,65(11):2257-2268
Animal cloning can be achieved by somatic cell nuclear transfer(SCNT), but the resulting live birth rate is relatively low. We previously improved the efficiency of bovine SCNT by exogenous melatonin treatment or by overexpression of lysine-specific demethylase 4D(KDM4D) and 4E(KDM4E). In this study, we revealed abundant alternative splicing(AS) transitions during fertilization and embryonic genome activation, and demonstrated abnormal AS in bovine SCNT embryos compared with in vitro fertilized ... 相似文献
262.
Hye Ran Park Jae Meen Lee Gwanhee Ehm Hui-Jun Yang In Ho Song Yong Hoon Lim Mi-Ryoung Kim Keyoung Ran Kim Woong-Woo Lee Young Eun Kim Jae Ha Hwang Chae Won Shin Hyeyoung Park Jin Wook Kim Han-Joon Kim Cheolyoung Kim Dong Gyu Kim Beom Seok Jeon Sun Ha Paek 《PloS one》2016,11(1)
Background
GPi (Internal globus pallidus) DBS (deep brain stimulation) is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia.Objectives
This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital.Methods
Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12–84)Results
The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006). The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073). When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement.Conclusions
GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center. 相似文献263.
Substitution of Ser113 for Gly113 in the cap domain of hydroxynitrile lyase from Manihot esculenta (MeHNL) was performed by site-directed mutagenesis to improve its self-generated folding and stability under denaturation conditions. The yield of the recombinant mutant HNL1 (mut-HNL1), which had higher specific activity than the wild type HNL0 (wt-HNL0), was increased by 2 to 3-fold. Thermostability of MeHNL was also enhanced, probably due to an increase in content of the -strand secondary structure according to CD analysis. Our data in this report suggest that Ser113 significantly contributes to the in vivo folding and stability of MeHNL and demonstrates an economic advantage of mut-HNL1 over the wt-HNL0. 相似文献
264.
Sun W Xing B Sun Y Du X Lu M Hao C Lu Z Mi W Wu S Wei H Gao X Zhu Y Jiang Y Qian X He F 《Molecular & cellular proteomics : MCP》2007,6(10):1798-1808
Hepatocellular carcinoma (HCC) is a highly malignant tumor, and chronic infection with hepatitis B virus is one of its major risk factors. To identify the proteins involved in HCC carcinogenesis, we used two-dimensional fluorescence DIGE to study the differentially expressed proteins in tumor and adjacent nontumor tissue samples. Samples from 12 hepatitis B virus-associated HCC patients were analyzed. A total of 61 spots were significantly up-regulated (ratio >/= 2, p = 0.01) in tumor samples, whereas 158 spots were down-regulated (ratio = -2, p = 0.01). Seventy-one gene products were identified among these spots. Members of the heat shock protein 70 and 90 families were simultaneously up-regulated, whereas metabolism-associated proteins were decreased in HCC samples. The down-regulation of mitochondrial and peroxisomal proteins in these results suggested loss of special organelle functions during HCC carcinogenesis. Four metabolic enzymes involved in the methylation cycle in the liver were down-regulated in HCC tissues, indicating S-adenosylmethionine deficiency in HCC. Two gene products, glyceraldehyde-3-phosphate dehydrogenase and formimidoyltransferase-cyclodeaminase, were identified from inversely altered spots, suggesting that different isoforms or post-translational modifications of these two proteins might play different roles in HCC. For the first time, the overexpression of Hcp70/Hsp90-organizing protein and heterogeneous nuclear ribonucleoproteins C1/C2 in HCC tissues was confirmed by Western blot and then by immunohistochemistry staining in 70 HCC samples, suggesting their potential as protein tumor markers. In summary, we profiled proteome alterations in HCC tissues, and these results may provide useful insights for understanding the mechanism involved in the process of HCC carcinogenesis. 相似文献
265.
Activated rheumatoid arthritis (RA) fibroblast-like synoviocytes (RAFLSs) play a central role in both initiating and driving
RA. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been documented to induce apoptosis only in a small
proportion of RAFLSs, which is followed by an induction of proliferation in surviving cells. Apigenin, a chemopreventive bioflavonoid,
exhibits proapoptotic activity in many types of cells. In the present study, we sought to determine whether apigenin could
enhance the cytotoxic effect of TRAIL on activated RAFLSs. Human RAFLSs isolated from patients with RA were treated with TRAIL
(1 nM), apigenin (20 μM), or their combination, and subjected to apoptosis analysis after a 24-h incubation and proliferation
analysis after a 72-h incubation. Apoptosis assay revealed that TRAIL or apigenin alone induced a marked apoptosis in RAFLS
and their combination yielded a synergistic increase in RAFLS apoptosis. Immunoblotting analysis of apoptosis regulators demonstrated
that combined treatment with apigenin increased caspase-3 expression and activity and decreased the Bcl-2/Bax ratio relative
to treatment with TRAIL alone. The presence of apigenin significantly restrained TRAIL-induced RAFLS proliferation, coupled
with restoration of the expression of two cell-cycle inhibitors p21 and p27. Moreover, the combination with apigenin blunted
TRAIL-induced activation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Our data collectively demonstrate that
apigenin sensitizes RAFLS to TRAIL-induced apoptosis and counteracts TRAIL-dependent RAFLS proliferation, which is likely
mediated through inactivation of PI3-K/Akt signaling pathway. 相似文献
267.
理解入侵生物的繁殖策略是阐明生物入侵机制的一个重要方面。入侵植物常表现出一些共同的繁殖特征, 如以两性花为主的性系统、自动自交为主的繁育系统或不依赖传粉媒介的无融合生殖和无性繁殖以及高生殖投资的资源配置策略等。成功入侵的外来植物通过影响本土的传粉者, 在种群和群落水平上影响本土植物的有性繁殖, 甚至促使某些本土植物在繁殖对策和表型性状上发生快速转变。目前, 入侵植物繁殖策略及其生态效应的研究多侧重于入侵种的快速演化, 而有关外来植物与本土植物间的相互影响及其可能存在的协同适应研究还较为缺乏。探讨本土植物在外来种入侵压力下的繁殖对策和响应机制, 将丰富人们对物种间竞争、共存及群落构建等机制的深入了解。从繁殖和适应的角度探求入侵植物与本土植物之间的复杂关系, 将有助于解析生物入侵的机制及人类干扰下的物种演化规律, 也为预测和防控入侵植物提供科学依据。 相似文献
268.
269.
Chang KH Multani PS Sun KH Vincent F de Pablo Y Ghosh S Gupta R Lee HP Lee HG Smith MA Shah K 《Molecular biology of the cell》2011,22(9):1452-1462
Nuclear fragmentation is a common feature in many neurodegenerative diseases, including Alzheimer's disease (AD). In this study, we show that nuclear lamina dispersion is an early and irreversible trigger for cell death initiated by deregulated Cdk5, rather than a consequence of apoptosis. Cyclin-dependent kinase 5 (Cdk5) activity is significantly increased in AD and contributes to all three hallmarks: neurotoxic amyloid-β (Aβ), neurofibrillary tangles (NFT), and extensive cell death. Using Aβ and glutamate as the neurotoxic stimuli, we show that deregulated Cdk5 induces nuclear lamina dispersion by direct phosphorylation of lamin A and lamin B1 in neuronal cells and primary cortical neurons. Phosphorylation-resistant mutants of lamins confer resistance to nuclear dispersion and cell death on neurotoxic stimulation, highlighting this as a major mechanism for neuronal death. Rapid alteration of lamin localization pattern and nuclear membrane change are further supported by in vivo data using an AD mouse model. After p25 induction, the pattern of lamin localization was significantly altered, preceding neuronal death, suggesting that it is an early pathological event in p25-inducible transgenic mice. Importantly, lamin dispersion is coupled with Cdk5 nuclear localization, which is highly neurotoxic. Inhibition of nuclear dispersion rescues neuronal cells from cell death, underscoring the significance of this event to Cdk5-mediated neurotoxicity. 相似文献
270.
Zhang LX Tong XJ Sun XH Tong L Gao J Jia H Li ZH 《Cellular and molecular neurobiology》2008,28(4):501-509
Objectives To observe the effect of ultrashortwave (USW) therapy on nerve regeneration after acellular nerve allografts(ANA) repairing
the sciatic nerve gap of rats and discuss its acting mechanisms. Methods Sixteen Wistar rats weighing 180–220 g were randomly divided into four groups with four rats in each group: normal control
group; acellular group (ANA, treated by hypotonic-chemical detergent, was applied for bridging a 10 mm-long sciatic nerve
defect); USW group (After 24 h of ANA repairing the sciatic nerve gap, low dose USW was administrated for 7 min, once a day,
20 times a course of treatment, three courses of treatment in all); and autografts group. 12 weeks after operation, a series
of examinations was performed, including electrophysiological methods, the restoring rate of tibialis anterior muscle wet
weight, histopathological observation (myelinated nerve number, myelin sheath thickness, and axon diameter), vascular endothelial
growth factor (VEGF) mRNA expression of spinal cord, and muscle at injury site, and analyzed statistically. Results Compared to acellular nerve allografts alone, USW therapy can increase nerve conductive velocity, the restoring rate of tibialis
anterior muscle wet weight, myelinated nerve number, axon diameter, VEGF mRNA expression of spinal cord, and muscle at injury
site, the difference is significant. There were no differences between USW group and autografts group except myelin sheath
thickness. Conclusions USW therapy can promote nerve axon regeneration and Schwann cells proliferation after ANA repairing the sciatic nerve gap
of rats, the upregulation of VEGF mRNA expression of spinal cord and muscle may play an important role. 相似文献