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971.
MacArthur BD Tare RS Murawski K Oreffo RO 《Biochemical and biophysical research communications》2008,377(1):68-72
Stem cell differentiation is controlled intrinsically by dynamic networks of interacting lineage-specifying and multipotency genes. However, the relationship between internal genetic dynamics and extrinsic regulation of internal dynamics is complex and, in the case of skeletal progenitor cell differentiation, incompletely understood. In this study we elucidate a set of candidate markers of multipotency in human skeletal progenitor cells by systematic study of the relationships between gene expression and environmental stimulus. We used full genome cDNA microarrays to explore gene expression profiles in skeletal progenitor enriched populations derived from adult human bone marrow, minimally cultured in basal, osteogenic, chondrogenic, and adipogenic lineage-specifying culture conditions. We then used a variety of statistical clustering procedures to identify a small subset of genes which are related to these stromal lineages but are specific to none. For a selection of 11 key genes, conclusions of the microarray study were confirmed using quantitative real-time PCR. 相似文献
972.
Voss AA Allen PD Pessah IN Perez CF 《Biochemical and biophysical research communications》2008,366(4):988-993
We studied cation regulation of wild-type ryanodine receptor type 1 (WTRyR1), type 3 (WTRyR3), and RyR3/RyR1 chimeras (Ch) expressed in 1B5 dyspedic myotubes. Using [3H]ryanodine binding to sarcoplasmic reticulum (SR) membranes, Ca2+ titrations with WTRyR3 and three chimeras show biphasic activation that is allosterically coupled to an attenuated inhibition relative to WTRyR1. Chimeras show biphasic Mg2+ inhibition profiles at 3 and 10 μM Ca2+, no observable inhibition at 20 μM Ca2+ and monophasic inhibition at 100 μM Ca2+. Ca2+ imaging of intact myotubes expressing Ch-4 exhibit caffeine-induced Ca2+ transients with inhibition kinetics that are significantly slower than those expressing WTRyR1 or WTRyR3. Four new aspects of RyR regulation are evident: (1) high affinity (H) activation and low affinity (L) inhibition sites are allosterically coupled, (2) Ca2+ facilitates removal of the inherent Mg2+ block, (3) WTRyR3 exhibits reduced cooperativity between H activation sites when compared to WTRyR1, and (4) uncoupling of these sites in Ch-4 results in decreased rates of inactivation of caffeine-induced Ca2+ transients. 相似文献
973.
Yang JH Wylie-Sears J Bischoff J 《Biochemical and biophysical research communications》2008,374(3):512-516
The endothelium of the cardiac valves is unique compared the rest of the vasculature in its ability to undergo an endothelial-to-mesenchymal transformation (EMT) in vitro in response to transforming growth factor-β (TGF-β). EMT is a critical event during embryonic valve development, and both VEGF-A and Notch1 have been shown to function in this process. Here we investigate the effects of VEGF-A and Notch1 on EMT in clonal endothelial cell (EC) populations isolated from adult aortic valve leaflets. VEGF-A inhibited TGF-β-induced EMT. Endothelial growth, however, was not affected by VEGF-A or TGF-β. A positive role for Notch1 was revealed in three experiments: (1) TGF-β induced Notch1 mRNA in valve ECs, (2) a γ-secretase inhibitor of Notch1 signaling blocked EMT, and (3) overexpression of a ligand-independent form of Notch1 induced EMT. These results demonstrate, for the first time, that VEGF-A and Notch1 play opposing roles in regulating EMT in post-natal valve endothelium. 相似文献
974.
复制缺陷型腺病毒载体介导hVEGF cDNA在C2C12和NIH3T3细胞中的表达 总被引:1,自引:0,他引:1
为提高hVEGFcDNA在心肌中的表达 ,降低在其它组织中表达可能产生的不良反应 ,用PCR法得到人磷酸肌酸激酶 (MCK)增强子和CMV核心启动子 .利用克隆技术构建了含双拷贝MCK增强子 (m)和人巨细胞病毒 (CMV)核心启动子 (c)的嵌合启动子 (mmc) ,构建真核表达质粒pK3 mmcLacZ ,制备受mmc嵌合启动子调控的重组腺病毒Ad mmcVEGF .经X gal染色、β 半乳糖苷酶定量分析、RT PCR、hVEGFELISA定量分析、VEGF活性测定等研究表明 ,mmc启动VEGF基因在小鼠肌细胞C2C12和NIH3T3细胞中能有效表达且具有一定的肌细胞特异表达功能 相似文献
975.
脊椎动物心肌基因表达的分子调控 总被引:1,自引:0,他引:1
鉴定在心脏发育过程中指导心脏形成的分子途径,将对心脏是如何形成和这些途径的打断如何导致先天性以及后天性心脏病的发生提供一个基本的认识,尽管脊椎动物骨骼肌和心肌看起来很相似,然而,它们的细胞谱系的特化和模式化是由不同的基因推动的,已知有几个转录因子家族在心肌发育和模式建成中发挥重要作用,包括MADS同源盒蛋白MEF2和SRF,螺旋-环-螺旋HAND因子,锌指GATA-4/5/6因子和NK-2同源异型因子,这些转录因子能激活心脏目标基因,从而调控心肌基因的表达. 相似文献
976.
巨噬细胞、内皮细胞对高密度脂蛋白的氧化修饰 总被引:6,自引:0,他引:6
为了探讨高密度脂蛋白 (HDL)在体内发生氧化修饰的部位及机制 ,分别观察了培养人动脉平滑肌细胞 (SMC)、动脉内皮细胞 (EC)及巨噬细胞 (MΦ)与HDL共同温育过程中 ,HDL的琼脂糖电泳相对迁移率 (REM)、硫代巴比妥酸反应物质 (TBARS)以及溶血卵磷脂 卵磷脂 (LPC PC)值等氧化指标的变化 .结果发现 ,HDL与 3种细胞温育 12h时 ,HDL几乎不发生氧化修饰 ,而HDL与MΦ和EC温育 2 4h后 ,其REM、TBARS、LPC PC值均显著上升 (p <0 0 1) ;而HDL与SMC温育后 ,其REM、TBARS值无显著改变 ,LPC PC值增加 (p <0 0 1) .结果提示 ,活体内HDL可能主要在动脉壁的内皮细胞及巨噬细胞的作用下发生氧化修饰 相似文献
977.
Chen Ling Zunpeng Liu Moshi Song Weiqi Zhang Si Wang Xiaoqian Liu Shuai Ma Shuhui Sun Lina Fu Qun Chu Juan Carlos Izpisua Belmonte Zhaoxia Wang Jing Qu Yun Yuan Guang-Hui Liu 《蛋白质与细胞》2019,10(4):249-271
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation.However,the underlying cellular and molecular mechanisms remain unidentified.Here,we generated non-integrative induced pluripotent stem cells(iPSCs)from fibroblasts of a CADASIL patient harboring a heterozygous NOTCH3 mutation(c.3226C>T,p.R1076C).Vascular smooth muscle cells(VSMCs)differentiated from CADASIL-specific iPSCs showed gene expression changes associated with disease phenotypes,including activation of the NOTCH and NF-kB signaling pathway,cytoskeleton disorganization,and excessive cell proliferation.In comparison,these abnormalities were not observed in vascular endothelial cells(VECs)derived from the patients iPSCs.Importantly,the abnormal upregulation of NF-kB target genes in CADASIL VSMCs was diminished by a NOTCH pathway inhibitor,providing a potential therapeutic strategy for CADASIL.Overall,using this iPSCbased disease model,our study identified clues for studying the pathogenic mechanisms of CADASIL and developing treatment strategies for this disease. 相似文献
978.
罗氏沼虾肌肉白浊病病原研究 总被引:14,自引:0,他引:14
从患白浊病的罗氏沼虾虾苗病灶分离到10多株菌株,其中一株经人工感染证实为病原菌,经ATB Expression自动细菌鉴定仪测试,为木糖葡萄球菌,其主要特性为拟球状(直径0.8-1.1μm),革兰氏阳性,无鞭毛,无荚膜,不产生芽孢,发酵葡萄糖、果糖、麦芽糖、乳糖、海藻糖、阿拉伯糖、蔗糖及甘露醇产酸,β-半乳糖甘酶、过氧化氢酶及脲酶阳性,氧化酶,血浆凝固醇、V-P反应,精氨酸双水解酶、鸟氨酸脱羧酶均为阴性。最适生长温度、盐度和pH值范围分别为28-37℃、0%-2%、6-9,对红霉素、卡那毒素、头孢氨苄及庆大霉素等药物敏感。 相似文献
979.
Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly.
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Vertebrate-striated muscle is assumed to owe its remarkable order to the molecular ruler functions of the giant modular signaling proteins, titin and nebulin. It was believed that these two proteins represented unique results of protein evolution in vertebrate muscle. In this paper we report the identification of a third giant protein from vertebrate muscle, obscurin, encoded on chromosome 1q42. Obscurin is approximately 800 kD and is expressed specifically in skeletal and cardiac muscle. The complete cDNA sequence of obscurin reveals a modular architecture, consisting of >67 intracellular immunoglobulin (Ig)- or fibronectin-3-like domains with multiple splice variants. A large region of obscurin shows a modular architecture of tandem Ig domains reminiscent of the elastic region of titin. The COOH-terminal region of obscurin interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin. Both proteins coassemble during myofibrillogenesis. During the progression of myofibrillogenesis, all obscurin epitopes become detectable at the M band. The presence of a calmodulin-binding IQ motif, and a Rho guanine nucleotide exchange factor domain in the COOH-terminal region suggest that obscurin is involved in Ca(2+)/calmodulin, as well as G protein-coupled signal transduction in the sarcomere. 相似文献
980.