全文获取类型
收费全文 | 29141篇 |
免费 | 2130篇 |
国内免费 | 1617篇 |
专业分类
32888篇 |
出版年
2024年 | 64篇 |
2023年 | 346篇 |
2022年 | 832篇 |
2021年 | 1407篇 |
2020年 | 966篇 |
2019年 | 1191篇 |
2018年 | 1167篇 |
2017年 | 830篇 |
2016年 | 1229篇 |
2015年 | 1897篇 |
2014年 | 2126篇 |
2013年 | 2286篇 |
2012年 | 2612篇 |
2011年 | 2287篇 |
2010年 | 1452篇 |
2009年 | 1235篇 |
2008年 | 1512篇 |
2007年 | 1328篇 |
2006年 | 1165篇 |
2005年 | 979篇 |
2004年 | 790篇 |
2003年 | 695篇 |
2002年 | 533篇 |
2001年 | 480篇 |
2000年 | 380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 15 毫秒
131.
The aim of this study was to investigate whether a moderate‐intensity static magnetic field (SMF) can enhance the killing effect of adriamycin (ADM) on K562 cells, and to explore the effects of SMF combined with ADM on K562 cells. We analyzed the metabolic activity of cells, cell cycle distribution, DNA damage, change in cell ultrastructure, and P‐glycoprotein (P‐gp) expression after K562 cells were exposed continuously to a uniform 8.8 mT SMF for 12 h, with or without ADM. Our results showed that the SMF combined with ADM (25 ng/ml) significantly inhibited the metabolic activity of K562 cells (P < 0.05), while neither ADM nor the SMF alone affected the metabolic activity of these cells. Cell ultrastructure was altered in the SMF + ADM group. For example, cell membrane was depressed, some protuberances were observable, and vacuoles in the cytoplasm became larger. Cells were arrested at the G2/M phase and DNA damage increased after cells were treated with the SMF plus ADM. ADM also induced the P‐gp expression. In contrast, in the SMF group and SMF + ADM group, the P‐gp expression was decreased compared with the ADM group. Taken together, our results showed that the 8.8 mT SMF enhanced the cytotoxity potency of ADM on K562 cells, and the decrease in P‐gp expression may be one reason underlying this effect. Bioelectromagnetics 32:191–199, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
132.
133.
134.
Sun G Hagooly A Xu J Nyström AM Li Z Rossin R Moore DA Wooley KL Welch MJ 《Biomacromolecules》2008,9(7):1997-2006
The in vivo behavior of shell cross-linked knedel-like (SCK) nanoparticles is shown to be tunable via a straightforward and versatile process that advances SCKs as attractive nanoscale carriers in the field of nanomedicine. Tuning of the pharmacokinetics was accomplished by grafting varied numbers of methoxy-terminated poly(ethylene glycol) (mPEG) chains to the amphiphilic block copolymer precursors, together with chelators for the radioactive tracer and therapeutic agent (64)Cu, followed by self-assembly into block copolymer micelles and chemical cross-linking throughout the shell regions. (64)Cu-radiolabeling was then performed to evaluate the SCKs in vivo by means of biodistribution experiments and positron emission tomography (PET). It was found that the blood retention of PEGylated SCKs could be tuned, depending on the mPEG grafting density and the nanoparticle surface properties. A semiquantitative model of the density of mPEG surface coverage as a function of in vivo behavior was applied to enhance the understanding of this system. 相似文献
135.
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136.
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
137.
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
138.
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
139.
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
140.