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981.
Selective inhibition of selenocysteine tRNA maturation and selenoprotein synthesis in transgenic mice expressing isopentenyladenosine-deficient selenocysteine tRNA
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Moustafa ME Carlson BA El-Saadani MA Kryukov GV Sun QA Harney JW Hill KE Combs GF Feigenbaum L Mansur DB Burk RF Berry MJ Diamond AM Lee BJ Gladyshev VN Hatfield DL 《Molecular and cellular biology》2001,21(11):3840-3852
Selenocysteine (Sec) tRNA (tRNA([Ser]Sec)) serves as both the site of Sec biosynthesis and the adapter molecule for donation of this amino acid to protein. The consequences on selenoprotein biosynthesis of overexpressing either the wild type or a mutant tRNA([Ser]Sec) lacking the modified base, isopentenyladenosine, in its anticodon loop were examined by introducing multiple copies of the corresponding tRNA([Ser]Sec) genes into the mouse genome. Overexpression of wild-type tRNA([Ser]Sec) did not affect selenoprotein synthesis. In contrast, the levels of numerous selenoproteins decreased in mice expressing isopentenyladenosine-deficient (i(6)A(-)) tRNA([Ser]Sec) in a protein- and tissue-specific manner. Cytosolic glutathione peroxidase and mitochondrial thioredoxin reductase 3 were the most and least affected selenoproteins, while selenoprotein expression was most and least affected in the liver and testes, respectively. The defect in selenoprotein expression occurred at translation, since selenoprotein mRNA levels were largely unaffected. Analysis of the tRNA([Ser]Sec) population showed that expression of i(6)A(-) tRNA([Ser]Sec) altered the distribution of the two major isoforms, whereby the maturation of tRNA([Ser]Sec) by methylation of the nucleoside in the wobble position was repressed. The data suggest that the levels of i(6)A(-) tRNA([Ser]Sec) and wild-type tRNA([Ser]Sec) are regulated independently and that the amount of wild-type tRNA([Ser]Sec) is determined, at least in part, by a feedback mechanism governed by the level of the tRNA([Ser]Sec) population. This study marks the first example of transgenic mice engineered to contain functional tRNA transgenes and suggests that i(6)A(-) tRNA([Ser]Sec) transgenic mice will be useful in assessing the biological roles of selenoproteins. 相似文献
982.
983.
984.
Zhang XQ Song J Rothblum LI Lun M Wang X Ding F Dunn J Lytton J McDermott PJ Cheung JY 《American journal of physiology. Heart and circulatory physiology》2001,281(5):H2079-H2088
The functional consequences of overexpression of rat heart Na+/Ca2+ exchanger (NCX1) were investigated in adult rat myocytes in primary culture. When maintained under continued electrical field stimulation conditions, cultured adult rat myocytes retained normal contractile function compared with freshly isolated myocytes for at least 48 h. Infection of myocytes by adenovirus expressing green fluorescent protein (GFP) resulted in >95% infection as ascertained by GFP fluorescence, but contraction amplitude at 6-, 24-, and 48-h postinfection was not affected. When they were examined 48 h after infection, myocytes infected by adenovirus expressing both GFP and NCX1 had similar cell sizes but exhibited significantly altered contraction amplitudes and intracellular Ca2+ concentration ([Ca2+]i) transients, and lower resting and diastolic [Ca2+]i when compared with myocytes infected by the adenovirus expressing GFP alone. The effects of NCX1 overexpression on sarcoplasmic reticulum (SR) Ca2+ content depended on extracellular Ca2+ concentration ([Ca2+]o), with a decrease at low [Ca2+]o and an increase at high [Ca2+]o. The half-times for [Ca2+]i transient decline were similar, suggesting little to no changes in SR Ca2+-ATPase activity. Western blots demonstrated a significant (P < or = 0.02) threefold increase in NCX1 but no changes in SR Ca2+-ATPase and calsequestrin abundance in myocytes 48 h after infection by adenovirus expressing both GFP and NCX1 compared with those infected by adenovirus expressing GFP alone. We conclude that overexpression of NCX1 in adult rat myocytes incubated at high [Ca2+]o resulted in enhanced Ca2+ influx via reverse NCX1 function, as evidenced by greater SR Ca2+ content, larger twitch, and [Ca2+]i transient amplitudes. Forward NCX1 function was also increased, as indicated by lower resting and diastolic [Ca2+]i. 相似文献
985.
Quezado Z Parent C Karzai W Depietro M Natanson C Hammond W Danner RL Cui X Fitz Y Banks SM Gerstenberger E Eichacker PQ 《American journal of physiology. Regulatory, integrative and comparative physiology》2001,281(4):R1177-R1185
We investigated whether decreases in circulating polymorphonuclear neutrophils (PMN) during lethal Escherichia coli (E. coli) sepsis in canines are related to insufficient host granulocyte colony-stimulating factor (G-CSF). Two-year-old purpose-bred beagles had intraperitoneal E. coli-infected or -noninfected fibrin clots surgically placed. By 10 to 12 h following clot, both infected survivors and nonsurvivors had marked increases (P = 0.001) in serum G-CSF levels (mean peak G-CSF ng/ml +/- SE, 1,931 +/- 364 and 2,779 +/- 681, respectively) compared with noninfected controls (134 +/- 79), which decreased at 24 to 48 h. Despite increases in G-CSF, infected clot placement caused delayed (P = 0.06) increases in PMN (mean +/- SE change from baseline in cells x 10(3)/mm(3) at 24 and 48 h) in survivors (+3.9 +/- 3.9 and +13.8 +/- 3.6) compared with noninfected controls (+13.1 +/- 2.8 and +9.1 +/- 2.5). Furthermore, infected nonsurvivors had decreases in PMN (-1.4 +/- 1.0 and -1.1 +/- 2.3, P = 0.006 compared with the other groups). We next investigated whether administration of G-CSF immediately after clot placement and continued for 96 h to produce more rapid and prolonged high levels of G-CSF after infection would alter PMN levels. Although G-CSF caused large increases in PMN compared with control protein from 2 to 48 h following clot in noninfected controls, it caused much smaller increases in infected survivors and decreases in infected nonsurvivors (P = 0.03 for the ordered effect of G-CSF comparing the three groups). Thus insufficient host G-CSF is unlikely the cause of decreased circulating PMN in this canine model of sepsis. Other factors associated with sepsis either alone or in combination with G-CSF itself may reduce increases or cause decreases in circulating PMN. 相似文献
986.
987.
Genistein对大鼠垂体前叶细胞增殖的抑制作用 总被引:2,自引:0,他引:2
应用细胞培养、^3H-TdR掺入、流式细胞和电镜技术,观察酪氨酸蛋白激酶(PTK)抑制剂genistein对正常大鼠垂体前叶细胞和垂体瘤细胞株AtT-20增殖的影响,并探讨其可能的机制。结果显示:genistein作用48h后可明显抑制正常大鼠垂体前叶细胞和垂体瘤细胞株AtT-20增殖。流式细胞仪检测发现,50和100μmol/L genistein可将AtT-20细胞阻断于G0/G1期及G2/M期,并出现凋亡峰,凋亡率分别灰19.9%和36.4%。电镜照片显示有凋亡细胞。结果表明,PTK抑制剂可以明显抑制正常大鼠垂体前叶细胞和垂体瘤细胞株AtT-20的殖,并诱导细胞凋亡,说明PTK活性对细胞增殖和分化有重要作用。 相似文献
988.
989.
Gαq/11介导的细胞信号转导在两肾一夹肾性高血压大鼠主动脉中的变化 总被引:3,自引:0,他引:3
实验以两肾一夹肾性高血压大鼠为模型,研究主动脉Gαq/11倡导 的细胞信号转导的变化及其意义。制备两肾一夹肾性高血压大鼠模型,分别于术后第1、2、4和8周测定动脉血压,用免疫印迹法检测主动脉组织中Gαq/11亚单位和细胞个信号调节激酶1/2(ERK1/2)含量,测定磷脂酶C(phospholipase C,PLC)活性。结果显示高血压组大鼠于术后第2周血压开始升高;主动脉Gαq/11和ERK1/2含量于术后第1周增加(分别为57.53%和40.16%),并维持在高水平(P<0.01);术后主动脉PLC活性亦增加(P<0.05)。实验表明,肾素依赖性高血压能引起大鼠主动脉Gαq/11介导的细胞信号转导系统激活,并参与高血压的发生和发展。 相似文献
990.
家兔脑干呼吸相关结构向斜方体后的轴突投射—CB—HRP逆行示踪研究 总被引:1,自引:0,他引:1
实验在10只成年家兔上进行,斜方体后核(RTN)内微量注入霍乱毒素β亚单位耦合辣根过氧化酶(CB-HRP)后,在脑桥Koelliker-Fuse 核,臂旁内侧核及臂旁外侧核观察到大量HRP标记神经元,在延髓孤束核腹外侧区,疑核和后疑核,面神经后核的腹侧及内侧区观察到少数HRP标记神经元,在面神经后核,疑核及后疑核区域观察到大量HRP顺行标记末梢纤维,实验结果表明,RTN和脑桥及延髓的呼吸相关结构之间存在纤维联系。 相似文献