全文获取类型
收费全文 | 12804篇 |
免费 | 981篇 |
国内免费 | 3篇 |
出版年
2023年 | 34篇 |
2022年 | 119篇 |
2021年 | 249篇 |
2020年 | 158篇 |
2019年 | 222篇 |
2018年 | 353篇 |
2017年 | 282篇 |
2016年 | 471篇 |
2015年 | 738篇 |
2014年 | 850篇 |
2013年 | 856篇 |
2012年 | 1165篇 |
2011年 | 1090篇 |
2010年 | 709篇 |
2009年 | 613篇 |
2008年 | 829篇 |
2007年 | 699篇 |
2006年 | 641篇 |
2005年 | 603篇 |
2004年 | 549篇 |
2003年 | 482篇 |
2002年 | 410篇 |
2001年 | 219篇 |
2000年 | 210篇 |
1999年 | 161篇 |
1998年 | 84篇 |
1997年 | 65篇 |
1996年 | 37篇 |
1995年 | 52篇 |
1994年 | 47篇 |
1993年 | 40篇 |
1992年 | 64篇 |
1991年 | 54篇 |
1990年 | 66篇 |
1989年 | 49篇 |
1988年 | 37篇 |
1987年 | 36篇 |
1986年 | 32篇 |
1985年 | 41篇 |
1984年 | 30篇 |
1983年 | 29篇 |
1982年 | 22篇 |
1981年 | 25篇 |
1979年 | 24篇 |
1977年 | 17篇 |
1974年 | 20篇 |
1973年 | 21篇 |
1971年 | 25篇 |
1970年 | 17篇 |
1968年 | 19篇 |
排序方式: 共有10000条查询结果,搜索用时 164 毫秒
951.
Kang NS Ahn JH Kim SS Chae CH Yoo SE 《Bioorganic & medicinal chemistry letters》2007,17(13):3716-3721
In order to obtain information regarding the design of selective DPP4 inhibitors, a 3D-QSAR study was conducted using DPP4, DPP8, and DPP9 inhibitors including newly synthesized six- and seven-membered cyclic hydrazine derivatives (KR64300, KR64301), which were evaluated in vitro for their inhibition of DPP4, DPP8, and DPP9. In this study, a highly predictive CoMFA model based on the fast-docking for DPP4, DPP8, and DPP9 inhibitors was obtained. This reliable model showed leave-one-out cross-validation q(2) and conventional r(2) values of 0.68 and 0.96 for the DPP4 inhibitors, 0.58 and 0.98 for the DPP8 inhibitors, and 0.68 and 0.97 for the DPP9 inhibitors, respectively. The validation of the CoMFA model was confirmed by the compounds in the test set, including the synthesized six- and seven-membered cyclic hydrazines. According to this study, to obtain selective DPP4 inhibitors compared to their isozymes, the interaction of the inhibitors with the S3 site and S1' site in DPP4 must be considered. The proposed newly synthesized compounds, KR64300 and KR64301, interact well with the sites mentioned above, showing excellent selectivity. 相似文献
952.
953.
A new study in this issue of Molecular Cell (Pleiss et al., 2007b) shows that changes in the environment rapidly alter the splicing efficiency of specific pre-mRNAs in yeast. 相似文献
954.
Gao Q Mezei G Nie Y Rao Y Choi CS Bechmann I Leranth C Toran-Allerand D Priest CA Roberts JL Gao XB Mobbs C Shulman GI Diano S Horvath TL 《Nature medicine》2007,13(1):89-94
Metabolic hormones, such as leptin, alter the input organization of hypothalamic circuits, resulting in increased pro-opiomelanocortin (POMC) tone, followed by decreased food intake and adiposity. The gonadal steroid estradiol can also reduce appetite and adiposity, and it influences synaptic plasticity. Here we report that estradiol (E2) triggers a robust increase in the number of excitatory inputs to POMC neurons in the arcuate nucleus of wild-type rats and mice. This rearrangement of synapses in the arcuate nucleus is leptin independent because it also occurred in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice, and was paralleled by decreased food intake and body weight gain as well as increased energy expenditure. However, estrogen-induced decrease in body weight was dependent on Stat3 activation in the brain. These observations support the notion that synaptic plasticity of arcuate nucleus feeding circuits is an inherent element in body weight regulation and offer alternative approaches to reducing adiposity under conditions of failed leptin receptor signaling. 相似文献
955.
Renal clearance of quantum dots 总被引:9,自引:0,他引:9
Choi HS Liu W Misra P Tanaka E Zimmer JP Itty Ipe B Bawendi MG Frangioni JV 《Nature biotechnology》2007,25(10):1165-1170
The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using intravenously administered quantum dots in rodents as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter by >15 nm and prevented renal excretion. A final hydrodynamic diameter <5.5 nm resulted in rapid and efficient urinary excretion and elimination of quantum dots from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications. 相似文献
956.
957.
Yoo JC Kim JH Ha JW Park NS Sohng JK Lee JW Park SC Kim MS Seong CN 《Journal of microbiology (Seoul, Korea)》2007,45(1):6-10
Culture broth of a streptomycete isolate, Streptomyces sp. CS684 showed antibacterial activity on methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE). Among purified substances from the organism, CSU-1, which is active against MRSA and VRE, is a C37H62O12Na (M+, 721.3875), and identified as laidlomycin. The anti-MRSA and anti-VRE activity of CSU-1 was stronger than oxacillin and vancomycin. Phylogenetic analysis showed that strain CS684 is very similar to Streptomyces ardus NRRL 2817T, whereas the ability of Streptomyces sp. CS684 to produce laidlomycin was shown to be unique. 相似文献
958.
Ryoo SW Park YK Park SN Shim YS Liew H Kang S Bai GH 《Journal of microbiology (Seoul, Korea)》2007,45(3):268-271
In Korea, the Mycobacterium tuberculosis K-strain is the most prevalent clinical isolates and belongs to the Beijing family. In this study, we conducted comparative porteomics of expressed proteins of clinical isolates of the K-strain with H37Rv, H37Ra as well as the vaccine strain of Mycobacterium bovis BCG following phagocytosis by the human monocytic cell line U-937. Proteins were analyzed by 2-D PAGE and MALDITOF-MS. Two proteins, Mb1363 (probable glycogen phosphorylase GlgP) and MT2656 (Haloalkane dehalogenase LinB) were most abundant after phagocytosis of M. tuberculosis K-strain. This approach provides a method to determine specific proteins that may have critical roles in tuberculosis pathogenesis. 相似文献
959.
Salmonella typhimurium, causing mouse typhoid, infects hosts such as macrophage cells, and proliferates in intracellular vacuoles causing infected cells to trigger numerous genes to respond against the infection. In this study, we tried to identify such genes in RAW264.7 cells by using the PCR screening method with degenerate primers. Fourteen genes were found to be differentially expressed after a 4 h infection in which the expression of 8 genes increased while expression of the others decreased. Most of the genes were involved in proinflammatory responses such as cytokines production and cell death. The mutation in msbB gene encoding the myristoyl transferase in lipid A of lipopolysaccharide (LPS) resulted in much lower toxicity to the inoculated animals. We compared the expression of the identified genes in wild-type and msbB-mutated S. typhimurium infections and found that Lyzs encoding lysozyme type M was differentially expressed. This gene is quite likely to be related to bacterial survival in the host cells. 相似文献
960.
Factors indicating culture status of two Spirulina platensis strains were monitored in a batch mode cultivation for 36 days. Changing mode in all factors showed a common turning point, indicating shift of cell or culture status. Mean biomass productivity was highly sustained until day 22, chlorophyll a concentration peaked on day 22, pH value was >12 on day 22, coil number was abruptly shortened on day 22, and floating activity was sustained at greater than 79% after day 22, indicating that day 22 is a criterion reflecting phase-transfer in cell physiology in a batch culture system. Many of these changes may have been caused by increased pH, suggesting that pH control is essential for mass production of S. platensis. Fluctuations in floating activity were likely induced by the number of cellular gas vacuoles. Consequently, coil number per trichome and floating activity of S. platensis could readily act as simple indicators for determination of culture status or harvesting time of cells. 相似文献