全文获取类型
收费全文 | 21074篇 |
免费 | 2099篇 |
国内免费 | 2515篇 |
专业分类
25688篇 |
出版年
2024年 | 79篇 |
2023年 | 327篇 |
2022年 | 645篇 |
2021年 | 993篇 |
2020年 | 717篇 |
2019年 | 903篇 |
2018年 | 808篇 |
2017年 | 596篇 |
2016年 | 808篇 |
2015年 | 1394篇 |
2014年 | 1557篇 |
2013年 | 1682篇 |
2012年 | 2044篇 |
2011年 | 1825篇 |
2010年 | 1241篇 |
2009年 | 1114篇 |
2008年 | 1318篇 |
2007年 | 1132篇 |
2006年 | 1032篇 |
2005年 | 872篇 |
2004年 | 759篇 |
2003年 | 698篇 |
2002年 | 606篇 |
2001年 | 323篇 |
2000年 | 309篇 |
1999年 | 275篇 |
1998年 | 207篇 |
1997年 | 136篇 |
1996年 | 116篇 |
1995年 | 93篇 |
1994年 | 120篇 |
1993年 | 79篇 |
1992年 | 112篇 |
1991年 | 81篇 |
1990年 | 65篇 |
1989年 | 71篇 |
1988年 | 58篇 |
1987年 | 59篇 |
1986年 | 49篇 |
1985年 | 41篇 |
1984年 | 58篇 |
1983年 | 37篇 |
1982年 | 33篇 |
1981年 | 29篇 |
1980年 | 16篇 |
1979年 | 32篇 |
1978年 | 25篇 |
1977年 | 21篇 |
1975年 | 17篇 |
1971年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
快速城市化导致城市及周边区域生态风险不断增加,认知城市化区域生态风险,探究其变化的驱动因素,提出行之有效的风险管控策略,对城市化区域生态环境与社会经济协调发展具有重要意义。以北京市为例,基于生态系统服务对生态风险进行了定量表征,分析了城市化因素对生态风险的驱动作用,探究了生态风险管控策略。研究结果表明:不透水地表扩张、经济增长、人口增长均对生态风险有显著的驱动作用,其中不透水地表扩张的驱动作用占主导地位。经济增长和人口增长通过影响不透水地表率间接作用于生态风险,在2005年时,人口密度对生态风险的驱动作用大于GDP强度,在2010年及之后,GDP强度对生态风险的驱动作用则变得比人口密度的驱动作用更大。北京市的生态风险管控策略为:在不透水地表率介于40%—70%的区域降低不透水地表率和实施土地利用及景观格局优化;不透水地表率大于70%的区域应防止不透水地表进一步扩张;不透水地表率低于40%的区域需通过提升生态系统质量、强化风险防范、降低风险暴露等途径来管控风险。此外,应通过提高海淀、昌平、通州、顺义等辖区的人口和经济城市化集约水平来降低生态风险。本研究阐明了城市化对区域生态风险的驱动作用... 相似文献
992.
Fei-Feng Li Ying Han Shuai Shi Xia Li Xi-Dong Zhu Jing Zhou Qing-Liang Shao Xue-Qi Li Shu-Lin Liu 《PloS one》2015,10(11)
Background
The human heart consists of several cell types with distinct lineage origins. Interactions between these cardiac progenitors are very important for heart formation. The muscle segment homeobox gene family plays a key role in the cell morphogenesis and growth, controlled cellular proliferation, differentiation, and apoptosis, but the relationships between the genetic abnormalities and CHD phenotypes still remain largely unknown. The aim of this work was to evaluate variations in MSX1 and MSX2 for their possible associations with CHD.Methods
We sequenced the MSX1 and MSX2 genes for 300 Chinese Han CHD patients and 400 normal controls and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE.Results
Six variations rs4647952, rs2048152, rs4242182, rs61739543, rs111542301 and rs3087539 were identified in the MSX2 gene, but the genetic heterozygosity of those SNPs was very low. In contrast, the genetic heterozygosity of two variations rs3821949 near the 5’UTR and rs12532 within 3’UTR of the MSX1 gene was considerably high. Statistical analyses showed that rs3821949 and rs12532 were associated with the risk of CHD (specifically VSD).Conclusions
The SNPs rs3821949 and rs12532 in the MSX1 gene were associated with CHD in Chinese Han populations. 相似文献993.
目的 探讨半夏总生物碱(total alkaloids from Pinellia Ternate,TAPT)对帕金森病模型大鼠的防治作用及其抗氧化机制.方法 采用脑内定位注射6-羟基多巴胺(6-OHDA)建立帕金森病大鼠模型,在模型建立成功的同时给予半夏总生物碱预防性治疗.采用Morris水迷宫进行帕金森病大鼠的行为学检测,用化学比色法检测大脑皮质及血清超氧化物歧化酶(SOD)活力、丙二醛(MDA)、过氧化氢(H2O2)和还原型谷胱甘肽(GSH)的含量.结果 与正常组比较,帕金森病模型组大鼠的逃避潜伏期明显延长(P<0.01),跨越平台次数明显减少(P<0.01);经半夏总生物碱治疗组,大鼠逃避潜伏期明显缩短(P<0.05,P<0.01),跨越平台次数明显增加(P<0.01).帕金森病模型组大鼠脑皮质及血清中MDA、H2O2的含量增加,SOD活性及GSH的含量降低(P<0.01);经半夏总生物碱治疗组,脑皮质MDA、H2O2的含量显著减少(P<0.01),皮质GSH、SOD含量显著增加(P<0.01);半夏总生物碱给药组中低浓度组、中浓度组血清MDA的含量无统计学意义(P>0.05),高浓度组血清MDA含量下降(P<0.01),各治疗组中血清H2O2含量明显下降(P<0.01),血清GSH含量显著增加(P<0.01).结论 半夏总生物碱具有改善学习记忆能力,对抗大鼠神经系统的退行性变有一定的作用,可能通过改变帕金森病模型大鼠皮质部分及血清SOD、GSH的含量,而抑制了MDA和H2O2的产生. 相似文献
994.
目的本实验旨在观察不同品系小鼠感染甲型流感病毒后肺组织内血栓形成的情况。方法使用H1N1病毒A/California/7/2009(CA7)株和H3N2病毒A/Brisbane/10/07株,对BALB/C小鼠、Scid小鼠、NOD/LTJ小鼠、BALB/C-nu小鼠、NOD-Scid小鼠和icosl-KO小鼠经乙醚麻醉后进行滴鼻攻毒。检测小鼠感染后肺组织病毒拷贝数并观察肺组织病理学改变。结果 H1N1和H3N2滴鼻攻毒的各组小鼠均染毒,病理表现为程度略有差异的间质性肺炎。13只H1N1病毒感染小鼠和6只H3N2感染小鼠在肺组织中观察到多个小血管内有血栓形成,血栓成分主要为纤维素和血小板。结论各品系小鼠感染H1N1和H3N2流感病毒后均可能出现肺组织内血栓形成。 相似文献
995.
杨树人工林生态系统通量贡献区分析 总被引:3,自引:1,他引:3
采取通量源区模型FSAM(Flux Source Area Model)利用2009年北京大兴区杨树人工林生态系统碳水通量涡度相关观测资料,分析了不同大气条件下生态系统的通量贡献区分布特征。研究结果表明:(1)该站通量贡献区随大气稳定条件增强而增大。除326.25°—3.75°方向生长季不稳定条件下外,生长季的通量贡献区范围普遍大于非生长季的贡献区范围;(2)通量贡献区与观测高度、冠层高度、地表粗糙度、风向以及大气稳定度有关,当风速风频较大,大气不稳定时,湍流扩散作用强烈,贡献区范围较小;(3)该观测场在2009年以不稳定大气条件为主,通量信息主要来源于距离观测塔50—400 m范围,且69.3%的信息来源于通量塔偏北风与偏南风方向,其中42.56%的信息来自于偏南风方向;(4)随着大气稳定程度加强,通量来源最少区从塔偏西方转为偏东方,在大气稳定度条件和风向的共同作用下,生长季时主要通量贡献区在塔偏南方向,而非生长季时主要通量贡献区在塔偏北方向。 相似文献
996.
Puping Liang Yanwen Xu Xiya Zhang Chenhui Ding Rui Huang Zhen Zhang Jie Lv Xiaowei Xie Yuxi Chen Yujing Li Ying Sun Yaofu Bai Zhou Songyang Wenbin Ma Canquan Zhou Junjiu Huang 《蛋白质与细胞》2015,6(5):363
Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing. 相似文献
997.
The preparation of novel steroidal heterocycles containing the 7-aryl-substituted 1,2,4-triazolo[1,5-a]pyrimidine moiety fused to the 16,17-positions of the steroid nucleus is described. The Aldol reaction of 4-aza-androst-3,17-dione (1a) and dehydroepiandrosterone (DHEA, 1b) with aromatic aldehydes was catalyzed by KF/Al(2)O(3) to give the corresponding 3-oxo-4-aza-5α- and 3β-hydroxy-5-en-16-arylidene-17-ketosteroids (2a-r). Subsequently, the intermediates 2a-r reacted with dinucleophilic 3-amino-1,2,4-triazole in presence of t-BuOK to afford the title compounds (3a-r). All the synthesized heterosteroids are new and are currently being evaluated for their biological activities. 相似文献
998.
Cherney DZ Reich HN Scholey JW Lai V Slorach C Zinman B Bradley TJ 《Canadian journal of physiology and pharmacology》2012,90(1):113-121
The protein kinase Cβ (PKCβ) system has been implicated in the deleterious vascular responses to hyperglycemia and angiotensin II (Ang?II) in experimental models of diabetes (DM). Whether these interactions are important in humans is unknown. Flow-mediated vasodilatation (FMD) was measured during clamped euglycemia and hyperglycemia, before and after randomization to PKCβ inhibition (ruboxistaurin; RBX, 32?mg daily, n = 13) or a placebo (n = 7) for 8?weeks in renin-angiotensin system (RAS) blockade-treated subjects with type 1 DM. Blood pressure responses to infused Ang?II were measured before and after randomization to RBX or a placebo. The RBX and placebo groups displayed similar clinical characteristics. Before RBX, FMD declined in response to hyperglycemia (6.8%?± 2.8% to 4.9%?± 1.8%). This effect was reversed after treatment with RBX (5.6%?± 3.1% to 6.0%?± 1.6% (within-group change, p = 0.009 (ANOVA)). No changes were observed in the placebo group. Infused Ang?II was associated with hypertensive responses in the RBX and placebo groups (p?< 0.05 (ANOVA)), and RBX did not influence this effect. In conclusion, RBX blunted the effect of hyperglycemia on FMD, suggesting that PKCβ may modulate endothelial function in type 1 DM. The lack of effect on Ang?II responses suggests that PKCβ inhibition may act through non-RAS pathways in humans with DM. 相似文献
999.
Beta-amyloid peptide (Aβ), a major protein component of senile plaques, has been considered as a critical cause in the pathogenesis
of Alzheimer’s disease (AD). Modulation of the Aβ-induced neurotoxicity has emerged as a possible therapeutic approach to
ameliorate the onset and progression of AD. The present study aimed to evaluate the protective effect of isorhynchophylline,
an oxindole alkaloid isolated from a Chinese herb Uncaria rhynchophylla, on Aβ-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that pretreatment with isorhynchophylline
significantly elevated cell viability, decreased the levels of intracellular reactive oxygen species and malondialdehyde,
increased the level of glutathione, and stabilized mitochondrial membrane potential in Aβ25-35-treated PC12 cells. In addition, isorhynchophylline significantly suppressed the formation of DNA fragmentation and the activity
of caspase-3 and moderated the ratio of Bcl-2/Bax. These results indicate that isorhynchophylline exerts a neuroprotective
effect against Aβ25-35-induced neurotoxicity in PC12 cells, at least in part, via inhibiting oxidative stress and suppressing the mitochondrial
pathway of cellular apoptosis. 相似文献
1000.
Nickens KP Han Y Shandilya H Larrimore A Gerard GF Kaldjian E Patierno SR Ceryak S 《Biochimica et biophysica acta》2012,1823(2):264-272
Acquisition of death-resistance is critical in the evolution of neoplasia. Our aim was to model the early stages of carcinogenesis by examining intracellular alterations in cells that have acquired apoptosis-resistance after exposure to a complex genotoxin. We previously generated sub-populations of BJ-hTERT human diploid fibroblasts, which have acquired death-resistance following exposure to hexavalent chromium [Cr(VI)], a broad-spectrum genotoxicant. Long-term exposure to certain forms of Cr(VI) is associated with respiratory carcinogenesis. Here, we report on the death-sensitivity of subclonal populations derived from clonogenic survivors of BJ-hTERT cells treated with 5 μM Cr(VI) (DR1, DR2), or selected by dilution-based cloning without treatment (CC1). Following Cr(VI) treatment, CC1 cells downregulated expression of the anti-apoptotic protein Bcl-2 and exhibited extensive expression of cleaved caspase 3. In contrast, the DR cells exhibited no cleaved caspase 3 expression and maintained expression of Bcl-2 following recovery from 24 h Cr(VI) exposure. The DR cells also exhibited attenuated mitochondrial-membrane depolarization and mitochondrial retention of cytochrome c and SMAC/DIABLO following Cr(VI) exposure. The DR cells exhibited less basal mtDNA damage, as compared to CC1 cells, which correlates with intrinsic (non-induced) death-resistance. Notably, there was no difference in p53 protein expression before or after treatment among all cell lines. Taken together, our data suggest the presence of more resilient mitochondria in death-resistant cells, and that death-resistance can be acquired in normal human cells early after genotoxin exposure. We postulate that resistance to mitochondrial-mediated cell death and mitochondrial dysregulation may be an initial phenotypic alteration observed in early stage carcinogenesis. 相似文献