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991.
Huang C Moree WJ Zamani-Kord S Li BF Tucci FC Malany S Wen J Wang H Hoare SR Yang C Madan A Crowe PD Beaton G 《Bioorganic & medicinal chemistry letters》2011,21(3):947-951
Structure-activity relationship studies were conducted to reduce CYP2D6-mediated metabolism in a series of indene H1-antihistamines. Reductions in pKa via incorporation of a β-fluoro substituent or a heteroaryl moiety were shown to reduce contributions to metabolism through this pathway. Several compounds, including 8l, 8o, and 12f were identified with promising primary in vitro profiles and reduced biotransformation via CYP2D6. 相似文献
992.
How males gain access to mates and the potential for female choice will determine whether polygyny can operate at several levels, from within litters and groups to the wider population. Female lesser flat-headed bats (Tylonycteris pachypus) form maternity groups in bamboo stems. Unusually for bats, they are multiparous, providing the opportunity to test whether multi-level polygyny differs among males depending on whether they roost with females, with males or are solitary. We genotyped 662 individuals from 54 internodes and analysed parentage of 165 litters. Our results revealed 170 sets of paternal twins/triplets, of which 96 were full-sibs and 74 were half-sibs. We found that males captured roosting with females typically sired more offspring overall than did other males and also showed a greater tendency to monopolize paternity within both litters and roosting groups. In comparison, males that sired fewer full-sibs were assigned more maternal half-sibs. These latter individuals, which included solitary males and those from all-male groups, might gain copulations either via roaming with furtive mating or during visits by females. Indeed, female lesser flat-headed bats store sperm, so could benefit from multiple mating to reduce genetic incompatibilities. At the same time, however, we found no evidence of outbreeding. Finally, relatedness and mtDNA analyses revealed that polygyny also operated within matrilineal kin, suggesting a system that might promote social cohesiveness. Future studies of individual movements will help to determine the extent to which mixed paternities in litters, matrilines and groups are driven by male or female behaviour. 相似文献
993.
Krupkin M Matzov D Tang H Metz M Kalaora R Belousoff MJ Zimmerman E Bashan A Yonath A 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2011,366(1580):2972-2978
Based on the presumed capability of a prebiotic pocket-like entity to accommodate substrates whose stereochemistry enables the creation of chemical bonds, it is suggested that a universal symmetrical region identified within all contemporary ribosomes originated from an entity that we term the 'proto-ribosome'. This 'proto-ribosome' could have evolved from an earlier machine that was capable of performing essential tasks in the RNA world, called here the 'pre-proto-ribosome', which was adapted for producing proteins. 相似文献
994.
Yamashita T Kamata M Endo S Yamamoto M Kakegawa K Watanabe H Miwa K Yamano T Funata M Sakamoto J Tani A Mol CD Zou H Dougan DR Sang B Snell G Fukatsu K 《Bioorganic & medicinal chemistry letters》2011,21(21):6314-6318
The co-crystal structure of the human acetyl-coenzyme A 2 (ACC2) carboxyl transferase domain and the reported compound CP-640186 (1b) suggested that two carbonyl groups are essential for potent ACC2 inhibition. By focusing on enhancing the interactions between the two carbonyl groups and the amino acid residues Gly(2162) and Glu(2230), we used ligand- and structure-based drug design to discover spirolactones bearing a 2-ureidobenzothiophene moiety. 相似文献
995.
Jin CH Krishnaiah M Sreenu D Subrahmanyam VB Rao KS Mohan AV Park CY Son JY Sheen YY Kim DK 《Bioorganic & medicinal chemistry letters》2011,21(20):6049-6053
A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphenyl)-3-(6-methylpyridin-2-yl)-1H-pyrazole-1-carbothioamide (14n) inhibited ALK5 phosphorylation with IC(50) value of 0.57 nM and showed 94% inhibition at 100 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. 相似文献
996.
Human saliva is a biological fluid with enormous diagnostic potential. Because saliva can be non-invasively collected, it provides an attractive alternative
for blood, serum or plasma. It has been postulated that the blood concentrations of many components are reflected in saliva. Saliva harbors a wide array of
proteins, which can be informative for the detection of diseases. Profiling the proteins in saliva over the course of disease progression could reveal
potential biomarkers indicative of different stages of diseases, which may be useful in medical diagnostics. With advanced instrumentation and developed
refined analytical techniques, proteomics is widely envisioned as a useful and powerful approach for salivary proteomic biomarker discovery. As
proteomic technologies continue to mature, salivary proteomics have great potential for biomarker research and clinical applications. The progress and
current status of salivary proteomics and its application in the biomarker discovery of oral and systematic diseases will be reviewed. The scientific and
clinical challenges underlying this approach will also be discussed. 相似文献
997.
Cao N Liao J Liu Z Zhu W Wang J Liu L Yu L Xu P Cui C Xiao L Yang HT 《Cell research》2011,21(9):1316-1331
The recent breakthrough in the generation of rat embryonic stem cells (rESCs) opens the door to application of gene targeting to create models for the study of human diseases. In addition, the in vitro differentiation system from rESCs into derivatives of three germ layers will serve as a powerful tool and resource for the investigation of mammalian development, cell function, tissue repair, and drug discovery. However, these uses have been limited by the difficulty of in vitro differentiation. The aims of this study were to establish an in vitro differentiation system from rESCs and to investigate whether rESCs are capable of forming terminal-differentiated cardiomyocytes. Using newly established rESCs, we found that embryoid body (EB)-based method used in mouse ESC (mESC) differentiation failed to work for the serum-free cultivated rESCs. We then developed a protocol by combination of three chemical inhibitors and feeder-conditioned medium. Under this condition, rESCs formed EBs, propagated and differentiated into three embryonic germ layers. Moreover, rESC-formed EBs could differentiate into spontaneously beating cardiomyocytes after plating. Analyses of molecular, structural, and functional properties revealed that rESC-derived cardiomyocytes were similar to those derived from fetal rat hearts and mESCs. In conclusion, we successfully developed an in vitro differentiation system for rESCs through which functional myocytes were generated and displayed phenotypes of rat fetal cardiomyocytes. This unique cellular system will provide a new approach to study the early development and cardiac function, and serve as an important tool in pharmacological testing and cell therapy. 相似文献
998.
999.
采用后组装法将非水溶性的治疗冠心病药物槲皮素组装进入MCM-41介孔分子筛的孔道中,药物组装率达37%[m(药物)/m(药物总量)],用XRD,扫描电镜和IR对药物组装体进行了表征;通过测定组装体在体外模拟人工小肠液中的溶出速率,表明制得了槲皮素/MCM-41缓释体系。 相似文献
1000.
目的比较关于家兔三种人工气道(artificial airway,AA)建立方法,为实验中快速建立家兔人工气道选择较好的方法提供参考。方法选用新西兰大耳白兔共30只,随机均分为3组。分别采用气管切开法、经口明视气管插管法、经口盲探气管插管法建立人工气道,比较各组建立人工气道的时间,首次成功率及并发症发生情况。结果经口盲探气管插管法建立人工气道的时间明显短于经口明视气管插管法和气管切开法,首次成功率由高到低依次是气管切开法、经口盲探气管插管法、经口明视气管插管法。经口盲探气管插管组并发症发生率最低,为(10±5)%,气管切开组和经口明视气管插管组并发症发生率分别为(20±10)%,(30±10)%。结论经口盲探气管插管是现阶段建立家兔人工气道时值得优先考虑的方法,简便易行、可操作性强,成功率高。 相似文献