全文获取类型
收费全文 | 7770篇 |
免费 | 644篇 |
国内免费 | 1篇 |
出版年
2023年 | 18篇 |
2022年 | 25篇 |
2021年 | 73篇 |
2020年 | 63篇 |
2019年 | 110篇 |
2018年 | 153篇 |
2017年 | 115篇 |
2016年 | 238篇 |
2015年 | 364篇 |
2014年 | 424篇 |
2013年 | 436篇 |
2012年 | 553篇 |
2011年 | 562篇 |
2010年 | 352篇 |
2009年 | 329篇 |
2008年 | 455篇 |
2007年 | 435篇 |
2006年 | 394篇 |
2005年 | 397篇 |
2004年 | 399篇 |
2003年 | 351篇 |
2002年 | 314篇 |
2001年 | 303篇 |
2000年 | 242篇 |
1999年 | 214篇 |
1998年 | 73篇 |
1997年 | 76篇 |
1996年 | 54篇 |
1995年 | 58篇 |
1994年 | 37篇 |
1993年 | 27篇 |
1992年 | 77篇 |
1991年 | 83篇 |
1990年 | 50篇 |
1989年 | 54篇 |
1988年 | 46篇 |
1987年 | 45篇 |
1986年 | 32篇 |
1985年 | 35篇 |
1984年 | 33篇 |
1982年 | 20篇 |
1981年 | 18篇 |
1979年 | 19篇 |
1978年 | 22篇 |
1977年 | 24篇 |
1976年 | 24篇 |
1974年 | 24篇 |
1973年 | 19篇 |
1971年 | 20篇 |
1970年 | 17篇 |
排序方式: 共有8415条查询结果,搜索用时 31 毫秒
1.
Yun-Hee Rhee Phil-Sang Chung Sung-Hoon Kim Jin Chul Ahn 《Biochemical and biophysical research communications》2014
Anethole has been known to have chemopreventive activities as a suppressor of the incidence and multiplicity of both invasive and noninvasive carcinomas. The goal of this study was to understand the anti-metastatic effect of anethole through C-X-C chemokine receptor type 4 (CXCR4)/tumor suppressor phosphatase and tensin homologue (PTEN) axis in DU145 prostate cancer cells. Anethole reduced both of the RNA level and the protein level of CXCR4 in a dose-dependent manner without cytotoxicity. Anethole also reduced the expression of CXCR4 and prolonged the expression of PTEN in DU145 prostate cancers. The phosphorylation of AKT and phosphatidylinositol-3kinase (PI3K) were decreased with anethole. The inhibition metastatic effect of anethole was arisen from down-regulating CXCR4 and up-regulating PTEN. Morphologically, anethole significantly inhibited the invasion of DU145 cell and down-regulated the activities of matrix-metalloproteinase (MMPs) in a dose-dependent manner. However, anethole didnot decrease the phosphorylation of PI3K and AKT while PTEN was silenced. Furthermore, the CXCR4 inhibition of anethole was not caused to proteasomal or lysosomal of CXCR4. 相似文献
2.
Development and characterization of a catalytically inactive cysteine protease domain of RtxA1/MARTXVv as a potential vaccine for Vibrio vulnificus 下载免费PDF全文
Recent studies have defined several virulence factors as vaccine candidates against Vibrio vulnificus. However, most of these factors have the potential to cause pathogenic effects in the vaccinees or induce incomplete protection. To overcome these drawbacks, a catalytically inactive form, CPDVv(C3725S), of the well‐conserved cysteine protease domain (CPD) of V. vulnificus multifunctional autoprocessing repeats‐in‐toxin (MARTXVv/RtxA1) was recombinantly generated and characterized. Notably, active and passive immunization with CPDVv(C3725S) conferred protective immunity against V. vulnificus strains. These results may provide a novel framework for developing safe and efficient subunit vaccines and/or therapeutics against V. vulnificus that target the CPD of MARTX toxins. 相似文献
3.
4.
5.
Kihoon Han Myoung-Hwan Kim Daniel Seeburg Jinsoo Seo Chiara Verpelli Seungnam Han Hye Sun Chung Jaewon Ko Hyun Woo Lee Karam Kim Won Do Heo Tobias Meyer Hyun Kim Carlo Sala Se-Young Choi Morgan Sheng Eunjoon Kim 《PLoS biology》2009,7(9)
Long-term depression (LTD) is a long-lasting activity-dependent decrease in synaptic strength. NMDA receptor (NMDAR)–dependent LTD, an extensively studied form of LTD, involves the endocytosis of AMPA receptors (AMPARs) via protein dephosphorylation, but the underlying mechanism has remained unclear. We show here that a regulated interaction of the endocytic adaptor RalBP1 with two synaptic proteins, the small GTPase RalA and the postsynaptic scaffolding protein PSD-95, controls NMDAR-dependent AMPAR endocytosis during LTD. NMDAR activation stimulates RalA, which binds and translocates widespread RalBP1 to synapses. In addition, NMDAR activation dephosphorylates RalBP1, promoting the interaction of RalBP1 with PSD-95. These two regulated interactions are required for NMDAR-dependent AMPAR endocytosis and LTD and are sufficient to induce AMPAR endocytosis in the absence of NMDAR activation. RalA in the basal state, however, maintains surface AMPARs. We propose that NMDAR activation brings RalBP1 close to PSD-95 to promote the interaction of RalBP1-associated endocytic proteins with PSD-95-associated AMPARs. This suggests that scaffolding proteins at specialized cellular junctions can switch their function from maintenance to endocytosis of interacting membrane proteins in a regulated manner. 相似文献
6.
Thomas Wiegand Wei-Chih Liao Ta Chung Ong Alexander Däpp Riccardo Cadalbert Christophe Copéret Anja Böckmann Beat H. Meier 《Journal of biomolecular NMR》2017,69(3):157-164
DNP (dynamic nuclear polarization)-enhanced solid-state NMR is employed to directly detect protein–DNA and protein–ATP interactions and identify the residue type establishing the intermolecular contacts. While conventional solid-state NMR can detect protein–DNA interactions in large oligomeric protein assemblies in favorable cases, it typically suffers from low signal-to-noise ratios. We show here, for the oligomeric DnaB helicase from Helicobacter pylori complexed with ADP and single-stranded DNA, that this limitation can be overcome by using DNP-enhanced spectroscopy. Interactions are established by DNP-enhanced 31P–13C polarization-transfer experiments followed by the recording of a 2D 13C–13C correlation experiment. The NMR spectra were obtained in less than 2 days and allowed the identification of residues of the motor protein involved in nucleotide binding. 相似文献
7.
Sitagliptin attenuates sympathetic innervation via modulating reactive oxygen species and interstitial adenosine in infarcted rat hearts 下载免费PDF全文
Tsung‐Ming Lee Wei‐Ting Chen Chen‐Chia Yang Shinn‐Zong Lin Nen‐Chung Chang 《Journal of cellular and molecular medicine》2015,19(2):418-429
We investigated whether sitagliptin, a dipeptidyl peptidase‐4 (DPP‐4) inhibitor, attenuates arrhythmias through inhibiting nerve growth factor (NGF) expression in post‐infarcted normoglycemic rats, focusing on adenosine and reactive oxygen species production. DPP‐4 bound adenosine deaminase has been shown to catalyse extracellular adenosine to inosine. DPP‐4 inhibitors increased adenosine levels by inhibiting the complex formation. Normoglycemic male Wistar rats were subjected to coronary ligation and then randomized to either saline or sitagliptin in in vivo and ex vivo studies. Post‐infarction was associated with increased oxidative stress, as measured by myocardial superoxide, nitrotyrosine and dihydroethidium fluorescent staining. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle‐treated infarcted rats compared with sham. Compared with vehicle, infarcted rats treated with sitagliptin significantly increased interstitial adenosine levels and attenuated oxidative stress. Sympathetic hyperinnervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis and western blotting and real‐time quantitative RT‐PCR of NGF. Arrhythmic scores in the sitagliptin‐treated infarcted rats were significantly lower than those in vehicle. Ex vivo studies showed a similar effect of erythro‐9‐(2‐hydroxy‐3‐nonyl) adenine (an adenosine deaminase inhibitor) to sitagliptin on attenuated levels of superoxide and NGF. Furthermore, the beneficial effects of sitagliptin on superoxide anion production and NGF levels can be reversed by 8‐cyclopentyl‐1,3‐dipropulxanthine (adenosine A1 receptor antagonist) and exogenous hypoxanthine. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation via adenosine A1 receptor and xanthine oxidase‐dependent pathways, which converge through the attenuated formation of superoxide in the non‐diabetic infarcted rats. 相似文献
8.
Sang Hee Han Jusong Kim Yerim Her Ikjoo Seong Sera Park Deepak Bhattarai Guanghai Jin Kyeong Lee Gukhoon Chung Sungkee Hwang Yun Soo Bae Jaesang Kim 《BMB reports》2015,48(12):691-695
We report that phytosphingosine, a sphingolipid found in many organisms and implicated in cellular signaling, promotes megakaryocytic differentiation of myeloid leukemia cells. Specifically, phytosphingosine induced several hallmark changes associated with megakaryopoiesis from K562 and HEL cells including cell cycle arrest, cell size increase and polyploidization. We also confirmed that cell type specific markers of megakaryocytes, CD41a and CD42b are induced by phytosphingosine. Phospholipids with highly similar structures were unable to induce similar changes, indicating that the activity of phytosphingosine is highly specific. Although phytosphingosine is known to activate p38 mitogen-activated protein kinase (MAPK)-mediated apoptosis, the signaling mechanisms involved in megakaryopoiesis appear to be distinct. In sum, we present another model for dissecting molecular details of megakaryocytic differentiation which in large part remains obscure. [BMB Reports 2015; 48(12): 691-695] 相似文献
9.
Golam Mezbah Uddin Chul Young Kim Donghwa Chung Kyung-A Kim Sang Hoon Jung 《BMB reports》2015,48(5):289-294
Caesalpinia sappan is a well-distributed plant that is cultivated in Southeast Asia, Africa, and the Americas. C. sappan has been used in Asian folk medicine and its extract has been shown to have pharmacological effects. Two homoisoflavonoids, sappanol and brazilin, were isolated from C. sappan by using centrifugal partition chromatography (CPC), and tested for protective effects against retinal cell death. The isolated homoisoflavonoids produced approximately 20-fold inhibition of N-retinylidene-N-retinyl-ethanolamine (A2E) photooxidation in a dose-dependent manner. Of the 2 compounds, brazilin showed better inhibition (197.93 ± 1.59 μM of IC50). Cell viability tests and PI/Hoechst 33342 double staining method indicated that compared to the negative control, sappanol significantly attenuated H2O2-induced retinal death. The compounds significantly blunted the up-regulation of intracellular reactive oxygen species (ROS), and sappanol inhibited lipid peroxidation in a concentration-dependent manner. Thus, both compounds represent potential antioxidant treatments for retinal diseases. [BMB Reports 2015; 48(5): 289-294] 相似文献
10.
Hack-Lyoung Kim Kwang Nam Jin Jae-Bin Seo Young Ho Choi Woo-Young Chung Sang-Hyun Kim Myung-A Kim Joo-Hee Zo 《PloS one》2015,10(4)
The aim of this study was to investigate whether brachial-ankle pulse wave velocity (baPWV) is associated with the severity of coronary artery disease (CAD) assessed by coronary computed tomography angiography (CCTA), and to evaluate baPWV as a predictor of obstructive CAD on CCTA. A total of 470 patients who underwent both baPWV and CCTA were included. We evaluated stenosis degree and plaque characteristics on CCTA. To estimate the severity of CAD, we calculated the number of segment with plaque (segment involvement score; SIS), stenosis degree-weighted plaque score (segment stenosis score; SSS), and coronary artery calcium score (CACS). The mean baPWV was 1,485 ± 315 cm/s (range, 935-3,175 cm/s). Non-obstructive (stenosis < 50%) and obstructive (stenosis ≥ 50%) CAD was found in 129 patients (27.4%) and 144 (30.6%), respectively. baPWV in patients with obstructive CAD was higher than that of patients with non-obstructive (1,680 ± 396 cm/s versus 1,477 ± 244 cm/s, P < 0.001) or no CAD (1,680 ± 396 cm/s versus ± 196 1,389 cm/s, P < 0.001). baPWV showed significant correlation with SSS (r = 0.429, P < 0.001), SIS (r = 0.395, P < 0.001), CACS (r 0.346, P < 0.001), and the number of segment with non-calcified plaque (r 0.092, P = 0.047), mixed plaque (r = 0.267, P < 0.001), and calcified plaque (r = 0.348, P < 0.001), respectively. The optimal baPWV cut-off value for the detection of obstructive CAD was 1,547 cm/s. baPWV ≥ 1,547 cm/s was independent predictor for the obstructive CAD. In conclusion, baPWV is well correlated with the severity of CAD evaluated by CCTA. baPWV has the potential to predict severity of coronary artery atherosclerosis. 相似文献