全文获取类型
收费全文 | 22269篇 |
免费 | 1975篇 |
国内免费 | 2566篇 |
出版年
2024年 | 61篇 |
2023年 | 219篇 |
2022年 | 556篇 |
2021年 | 890篇 |
2020年 | 758篇 |
2019年 | 897篇 |
2018年 | 860篇 |
2017年 | 702篇 |
2016年 | 833篇 |
2015年 | 1294篇 |
2014年 | 1638篇 |
2013年 | 1770篇 |
2012年 | 2120篇 |
2011年 | 1968篇 |
2010年 | 1316篇 |
2009年 | 1168篇 |
2008年 | 1535篇 |
2007年 | 1292篇 |
2006年 | 1204篇 |
2005年 | 996篇 |
2004年 | 982篇 |
2003年 | 908篇 |
2002年 | 812篇 |
2001年 | 369篇 |
2000年 | 265篇 |
1999年 | 215篇 |
1998年 | 218篇 |
1997年 | 132篇 |
1996年 | 129篇 |
1995年 | 130篇 |
1994年 | 94篇 |
1993年 | 77篇 |
1992年 | 64篇 |
1991年 | 46篇 |
1990年 | 31篇 |
1989年 | 44篇 |
1988年 | 28篇 |
1987年 | 27篇 |
1986年 | 28篇 |
1985年 | 25篇 |
1984年 | 7篇 |
1983年 | 10篇 |
1982年 | 18篇 |
1981年 | 5篇 |
1977年 | 5篇 |
1969年 | 4篇 |
1967年 | 4篇 |
1965年 | 4篇 |
1963年 | 3篇 |
1962年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
921.
恩诺沙星在罗氏沼虾体内的药物代谢动力学 总被引:5,自引:0,他引:5
应用反相高效液相色谱法(RP-HPLC)研究了恩诺沙星在罗氏沼虾(Macrobrachiumrosenbergii)体内的药物代谢动力学。实验结果表明,恩诺沙星在血淋巴、肝胰腺、肌肉中的平均回收率分别为86.54%±2.39%、85.43%±2.75%、95.01%±1.99%,其代谢产物环丙沙星在血淋巴、肝胰腺、肌肉中的平均回收率分别为94.34%±8.30%、75.17%±5.42%、80.42%±1.67%;恩诺沙星及其代谢产物环丙沙星在三种组织中的平均日内精密度分别为3.39%±0.53%和3.92%±1.24%,而日间精密度分别为5.11%±1.73%和5.28%±2.10%。恩诺沙星、环丙沙星的最低检测限分别为0.02μg/ml和0.01μg/ml。罗氏沼虾以10mg/kg虾体重剂量单次肌肉注射给药后,血液中药物浓度即刻达到峰值,并迅速向组织中分布。实验数据经MCPKP药动学软件分析,恩诺沙星在血淋巴中的主要药物代谢动力学参数为:t1/2α为0.581h、t1/2β为69.315h、Vd/F为7.230L/kg、CL/F为0.035L/h.kg、K12为0.01/h、K21为0.005/h、AUC为291.898μg/ml.h、Tmax为0.083h、Cmax为6.293μg/ml;恩诺沙星在肝胰腺、肌肉组织中主要药动学参数:t1/2α为1.941h、0.000h;t1/2β为70.732h、59.456h;AUC为308.07μg/ml.h、217.039μg/ml.h。三种组织中均能检测到恩诺沙星的活性代谢产物环丙沙星,但含量均处于较低水平,药物浓度-时间数据经MCPKP药动学软件处理后,不能用开放性一室模型或二室模型拟合。 相似文献
922.
Comparisons of vertebrate mitochondrial genomes(mitogenomes) may yield significant insights into the evolution of organisms and genomes. However,no complete mitogenome from the snake family Psammophiidae has been reported. In this study, we sequenced and annotated the complete mitogenome of Psammophis lineolatus, representing the first mitogenome of Psammophiidae. The total length is 17 166 bp,consisting of 13 protein-coding genes(PCGs), 22 transfer RNAs(tRNAs), two ribosomal RNAs(12 S rRNA and16 S rRNA), and duplicate control regions(CRs). This gene arrangement belongs to the Type Ⅲ pattern,which is a widely shared gene order in Alethinophidian snakes. All tRNAs exhibit cloverleaf structures with the exception of tRNA-SerAGY and tRNA-Pro, which lack a dihydrouridine(DHU) arm/stem and TΨC loop,respectively. The 13 PCGs include five start codons(ATG,GTG, ATA, ATT, and ATC), two complete stop codons(TAA and AGG), and two incomplete stop codon(T--and TA-). In addition, the Ka/Ks ratios indicate that all PCGs had undergone a strong purifying selection.Four types of CR domains rearrangement occurred among eight species of Elapoidea. The phylogenetic reconstructions with both Bayesian inference and maximum likelihood methods support the placement of Psammophiidae in the Elapoidea superfamily,with Homalopsidae being the sister taxon to Elapoidea and Colubroidea. However, the sister taxon of Psammophiidae is unclear due to the availability of Elapoidea mitogenomes being limited to the family Elapidae. More mitogenomes from different taxonomic groups in Elapoidea are needed to better understand the phylogenetic relationships within Elapoidea. 相似文献
923.
Feng Guo Chengchun Tang Bo Huang Lifei Gu Jun Zhou Zongyang Mo Chang Liu Yuqing Liu 《Molecules and cells》2022,45(3):122
The aim of this study was to investigating whether lncRNA H19 promotes myocardial fibrosis by suppressing the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β axis. Patients with atrial fibrillation (AF) and healthy volunteers were included in the study, and their biochemical parameters were collected. In addition, pcDNA3.1-H19, si-H19, and miR-29a/b-3p mimic/inhibitor were transfected into cardiac fibroblasts (CFs), and proliferation of CFs was detected by MTT assay. Expression of H19 and miR-29a/b-3p were detected using real-time quantitative polymerase chain reaction, and expression of α-smooth muscle actin (α-SMA), collagen I, collagen II, matrix metalloproteinase-2 (MMP-2), and elastin were measured by western blot analysis. The dual luciferase reporter gene assay was carried out to detect the sponging relationship between H19 and miR-29a/b-3p in CFs. Compared with healthy volunteers, the level of plasma H19 was significantly elevated in patients with AF, while miR-29a-3p and miR-29b-3p were markedly depressed (P < 0.05). Serum expression of lncRNA H19 was negatively correlated with the expression of miR-29a-3p and miR-29b-3p among patients with AF (rs = –0.337, rs = –0.236). Moreover, up-regulation of H19 expression and down-regulation of miR-29a/b-3p expression facilitated proliferation and synthesis of extracellular matrix (ECM)-related proteins. SB431542 and si-VEGFA are able to reverse the promotion of miR-29a/b-3p on proliferation of CFs and ECM-related protein synthesis. The findings of the present study suggest that H19 promoted CF proliferation and collagen synthesis by suppressing the miR-29a-3p/miR-29b-3p-VEGFA/TGF-β axis, and provide support for a potential new direction for the treatment of AF. 相似文献
924.
Yohei Takahashi Haruaki Ishiyama Takaaki Kubota Jun’ichi Kobayashi 《Bioorganic & medicinal chemistry letters》2010,20(14):4100-4103
A new β-carboline alkaloid, eudistomidin G (1), has been isolated from the Okinawan marine tunicate Eudistoma glaucus, and the structure was elucidated from spectroscopic data. Furthermore, the structure of eudistomidin B (2), which has been isolated from the same tunicate, was revised from 2a to 2b by detailed analyses of spectroscopic data. Asymmetric synthesis of the revised structure (2b) of eudistomidin B (2) and its (1S,10S)-diastereomer (2c) has been accomplished with the Noyori catalytic asymmetric hydrogen-transfer reaction. The absolute configuration of eudistomidin B (2) was confirmed to be 2b possessing (1R,10S)-configuration, from comparison of the 1H NMR data, CD spectra, [α]D values, and HPLC analysis of 2b, 2c, and natural eudistomidin B. 相似文献
925.
Jin‐Shu Yang Hiromichi Nagasawa Yoshihiro Fujiwara Shinji Tsuchida Wei‐Jun Yang 《Zoologica scripta》2010,39(6):621-630
Yang, J.‐S., Nagasawa, H., Fujiwara, Y., Tsuchida, S. & Yang, W.‐J. The complete mitogenome of the hydrothermal vent crab Gandalfus yunohana (Crustacea: Decapoda: Brachyura): a link between the Bythograeoidea and Xanthoidea. —Zoologica Scripta, 39, 621–630. Metazoan mitochondrial genomes (mitogenomes) are often used for all‐level phylogenetic analyses and evolution modelling. Although mitochondrial fragments facilitate studying the occurrence and dispersal of hydrothermal‐vent species, few complete mitogenomes have been determined for comprehensive analyses. We determined the complete nucleotide sequence of the bythograeid crab Gandalfus yunohana. The G. yunohana mitogenome is 15 567 bp in length and with an AT content of 69.9%. A putative control region of 625 bp was identified due to its position (between rrnS and trnI) and AT richness (72.8%), which exhibits high similarity with that of the Australian giant crab Pseudocarcinus gigas. The mitochondrial gene order is identical to the typical brachyuran mode. Codon usage, nucleotide composition and bias are well conserved as the Brachyura. Phylogenetic analyses from protein‐coding genes indicated its closest relationship with P. gigas. All the results support the close evolution distance between the Bythograeoidea and Xanthoidea, which might imply the possible origin that the only superfamily of vent crabs underwent. The G. yunohana mitogenome exhibits highly conserved characteristics with those of other decapods, especially its close relative brachyurans. A recent origin rather than the relic fauna was suggested. The present study will supply considerable data of use for both genomics and evolutionary research on hydrothermal vent ecosystems. 相似文献
926.
The effect of inorganic salts on the hydrolysis of starch in a microwave field was investigated and it was found that some inorganic salts can effectively accelerate the acid hydrolysis of starch. The yield of D-glucose reached 111 wt% (equal to the theoretical yield). 相似文献
927.
The ribonuclease III superfamily represents a structurally related group of double-strand (ds) specific endoribonucleases which play key roles in diverse prokaryotic and eukaryotic RNA maturation and degradation pathways. A dsRNA-binding domain (dsRBD) is a conserved feature of the superfamily and is important for substrate recognition. RNase III family members also exhibit a "catalytic" domain, in part defined by a set of highly conserved amino acids, of which at least one (a glutamic acid) is important for cleavage but not for substrate binding. However, it is not known whether the catalytic domain requires the dsRBD for activity. This report shows that a truncated form of Escherichia coli RNase III lacking the dsRBD (RNase III[DeltadsRBD]) can accurately cleave small processing substrates in vitro. Optimal activity of RNase III[DeltadsRBD] is observed at low salt concentrations (<60 mM Na(+)), either in the presence of Mg(2+) (>25 mM) or Mn(2+) ( approximately 5 mM). At 60 mM Na(+) and 5 mM Mn(2+) the catalytic efficiency of RNase III[DeltadsRBD] is similar to that of RNase III at physiological salt concentrations and Mg(2+). In the presence of Mg(2+) RNase III[DeltadsRBD] is less efficient than the wild-type enzyme, due to a higher K(m). Similar to RNase III, RNase III[DeltadsRBD] is inhibited by high concentrations of Mn(2+), which is due to metal ion occupancy of an inhibitory site on the enzyme. RNase III[DeltadsRBD] retains strict specificity for dsRNA, as indicated by its inability to cleave (rA)(25), (rU)(25), or (rC)(25). Moreover, dsDNA, ssDNA, or an RNA-DNA hybrid are not cleaved. Low (micromolar) concentrations of ethidium bromide block RNase III[DeltadsRBD] cleavage of substrate, which is similar to the inhibition seen with RNase III and is indicative of an intercalative mode of inhibition. Finally, RNase III[DeltadsRBD] is sensitive to specific Watson-Crick base-pair substitutions which also inhibit RNase III. These findings support an RNase III mechanism of action in which the catalytic domain (i) can function independently of the dsRBD, (ii) is dsRNA-specific, and (iii) participates in cleavage site selection. 相似文献
928.
Choi KS Jun HS Kim HN Park HJ Eom YW Noh HL Kwon H Kim HM Yoon JW 《Journal of virology》2001,75(4):1949-1957
Soluble mediators such as interleukin-1beta, tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) produced from activated macrophages play an important role in the destruction of pancreatic beta cells in mice infected with a low dose of the D variant of encephalomyocarditis (EMC-D) virus. The tyrosine kinase signaling pathway was shown to be involved in EMC-D virus-induced activation of macrophages. This investigation was initiated to determine whether the Src family of kinases plays a role in the activation of macrophages, subsequently resulting in the destruction of beta cells, in mice infected with a low dose of EMC-D virus. We examined the activation of p59/p56(Hck), p55(Fgr), and p56/p53(Lyn) in macrophages from DBA/2 mice infected with the virus. We found that p59/p56(Hck) showed a marked increase in both autophosphorylation and kinase activity at 48 h after infection, whereas p55(Fgr) and p56/p53(Lyn) did not. The p59/p56(Hck) activity was closely correlated with the tyrosine phosphorylation level of Vav. Treatment of EMC-D virus-infected mice with the Src kinase inhibitor, PP2, resulted in the inhibition of p59/p56(Hck) activity and almost complete inhibition of the production of TNF-alpha and iNOS in macrophages and the subsequent prevention of diabetes in mice. On the basis of these observations, we conclude that the Src kinase, p59/p56(Hck), plays an important role in the activation of macrophages and the subsequent production of TNF-alpha and nitric oxide, leading to the destruction of pancreatic beta cells, which results in the development of diabetes in mice infected with a low dose of EMC-D virus. 相似文献
929.
Capsaicin inhibits the voltage-operated calcium channels intracellularly in the antral circular myocytes of guinea-pig stomach 总被引:1,自引:0,他引:1
Studies of the effect of capsaicin (CAP) on the smooth muscle contractions have shown both contraction and relaxation in various preparations. The direct effect of CAP on gastric smooth muscle itself has not yet been reported, though CAP was reported to relax the isolated guinea-pig stomach by releasing nitric oxide from the CAP-sensitive sensory neurons. Here we showed an evidence that CAP evokes a prolonged relaxation of gastric antral circular smooth muscle (CAP-induced relaxation) by blocking the voltage-operated Ca2+ channels (VOCC) from inside of the cell. CAP suppressed dose-dependently the spontaneous contractions of guinea-pig gastric circular muscle strip under the condition without neural influence (IC50 = 5.8 microM). The inhibitory effects of CAP both on the high K+ contracture induced by 50 mM K+ Tyrode solution and on the slow waves recorded using a conventional intracellular microelectrode technique were similar to those of Ca2+ channel antagonists, indicating that Ca2+ influx through the VOCC is decreased by CAP. Ca2+ channel current (I(Ba)) decreased in a concentration-dependent manner on superfusing the physiological salt solution containing various concentrations of CAP. The steady-state activation and inactivation curves of I(Ba) were not affected by the treatment with CAP. The experiment using a synthetic water-soluble analog of CAP, DA-5018 x HCl, suggested that the acting site of CAP is present in the intracellular side. Spontaneous transient outward K+ currents (STOCs) recorded at a holding potential of 0 mV were also inhibited by CAP and verapamil, Ca channel blocker. Taken together, these results indicate that CAP-induced relaxation is associated with the direct inhibitory action on the VOCC from inside of the cell. 相似文献
930.
在大鳞Lizamacrolepis鳃上检获到鲻鱼虫属1新种,小钩鲻鱼虫,新种LigophorushamulosusPan&Zhang,sp.nov.。以其后吸器两对中央大钩的形态结构以及背、腹中央大钩量度上的差异,背联结片的结构和交接器形态结构不同而区别于LigophorusimitansEuzet&Suriano,1977。 相似文献