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131.
Guowei Jiang Asuka Inoue Junken Aoki Glenn D. Prestwich 《Bioorganic & medicinal chemistry letters》2013,23(6):1865-1869
We describe an efficient synthesis of metabolically stabilized sn-2 radyl phosphorothioate analogs of lysophosphatidic acid (LPA), and the determination of the agonist activity of each analog for the six LPA receptors (LPA1–6) using a recently developed TGFα shedding assay. In general, the sn-2 radyl OMPT analogs showed similar agonist activities to the previous 1-oleoyl-2-O-methyl-glycerophosphothioate (sn-1 OMPT) analogs for LPA1–6 receptors. In most cases, the sn-2 radyl-OMPT analogs were more potent agonists than LPA itself. Most importantly, sn-2 alkyl OMPT analogs were very potent LPA5 and LPA6 agonists. The availability of sn-2 radyl OPMT analogs further refines the structure–activity relationships for ligand–receptor interactions for this class of GPCRs. 相似文献
132.
Rong Jiang Bozena Frackowiak Youseung Shin Xinyi Song Weimin Chen Li Lin Michael D. Cameron Derek R. Duckett Theodore M. Kamenecka 《Bioorganic & medicinal chemistry letters》2013,23(9):2683-2687
Starting from pyrazole HTS hit (1), a series of 1-aryl-1H-indazoles have been synthesized as JNK3 inhibitors with moderate selectivity against JNK1. SAR studies led to the synthesis of 5r as double digital nanomolar JNK3 inhibitor with good in vivo exposure. 相似文献
133.
Tian-Xing Shi Shu Wang Ke-Wu Zeng Peng-Fei Tu Yong Jiang 《Bioorganic & medicinal chemistry letters》2013,23(21):5904-5908
Five new phenolic glycosides, tenuisides A–E (1?5), and a new megastigmane glycoside, tenuiside F (6), along with seventeen known compounds (7–23) were isolated from the aerial parts of Polygala tenuifolia Willd. Their structures were established by detailed analysis of NMR and HRESIMS spectroscopic data, and the absolute configurations of compounds 5 and 6 were determined by CD spectra and in-NMR-tube Mosher’s method. The inhibitory effects of these compounds were evaluated on NO production in LPS-activated BV-2 microglia cells. Compound 17 showed the strongest activity, with an IC50 value of 7.4 μM, while compounds 1, 8, 14, and 18 showed the moderate activities, with IC50 values of 16.2–38.5 μM. And their primary structure–activity relationships (SARs) of NO inhibitory effects were also briefly discussed. 相似文献
134.
Qiao Sun Yiwu Yao Chunping Liu Hua Li Hequan Yao Xiaowen Xue Jinsong Liu Zhengchao Tu Sheng Jiang 《Bioorganic & medicinal chemistry letters》2013,23(11):3295-3299
We report the design, synthesis, and biological evaluation of a new series of HDAC1 inhibitors using click chemistry. Compound 17 bearing a phenyl ring at meta-position was identified to show much better selectivity for HDAC1 over HDAC7 than SAHA. The compond 17 also showed better in vitro anticancer activities against several cancer cell lines than that of SAHA. This work could serve as a foundation for further exploration of selective HDAC inhibitors using the compound 17 molecular scaffold. 相似文献
135.
MOC-31和CD44v6在良恶性腹水鉴别诊断中的应用 总被引:1,自引:0,他引:1
目的探讨检测肿瘤标志物MOC-31和CD44v6对鉴别良恶性腹水的诊断价值。方法利用液基薄层细胞学自动涂片技术方法筛查出查到肿瘤细胞的恶性腹水标本390例以及良性腹水标本100例,分别采用酶联免疫吸附法(ELISA)和免疫细胞化学染色检测MOC-31和CD44v6的含量和表达情况。结果 ELISA结果显示MOC-31和CD44v6在良性腹水中的含量分别为21±4ng/ml和291±32ng/ml,在恶性腹水中的含量分别为98.1±19.3ng/ml和891±116ng/ml,差异均具有显著性(P<0.05);免疫细胞化学染色显示MOC-31在恶性腹水细胞中阳性表达250例,良性腹水细胞中阳性表达5例;CD44v6在恶性腹水细胞中阳性表达266例,良性腹水细胞中阳性表达3例,差异均具有显著性(P<0.05)。结论 MOC-31和CD44v6可以做为良恶性腹水鉴别诊断的重要指标,值得在临床病理工作中推广应用。 相似文献
136.
Lili Ji Ping Jiang Bin Lu Yuchen Sheng Xin Wang Zhengtao Wang 《The Journal of nutritional biochemistry》2013,24(11):1911-1919
Chlorogenic acid (CGA) is one of the most abundant dietary polyphenols, possessing well-known antioxidant capacity. The present study is designed to observe the protection provided by CGA against acetaminophen (AP)-induced liver injury in mice in vivo and the underlying mechanisms engaged in this process. Serum transaminases analysis and liver histological evaluation demonstrated the protection of CGA against AP-induced liver injury. CGA treatment decreased the increased number of liver apoptotic cells induced by AP in a dose-dependent manner. CGA also inhibited AP-induced cleaved activation of caspase-3, 7. Moreover, CGA reversed AP-decreased liver reduced glutathione (GSH) levels, glutamate-cysteine ligase (GCL) and glutathione reductase activity. Further results showed that CGA increased mRNA and protein expression of the catalytic subunit of GCL (GCLC), thioredoxin (Trx) 1/2 and thioredoxin reductase (TrxR) 1. Furthermore, CGA abrogated AP-induced phospholyated activation of ERK1/2, c-Jun N-terminal kinase (JNK), p38 kinases and molecular signals upstream. The results of this study demonstrate that CGA counteracts AP-induced liver injury at various levels by preventing apoptosis and oxidative stress damage, and more specifically, both the GSH and Trx antioxidant systems and the mitogen-activated protein kinase (MAPK) signaling cascade appear to be engaged in this protective mechanism. 相似文献
137.
Yanfei Jiang Yujie Li Ye Ding Xiaoqian Dai Xiaotao Ma Lei Bao 《Bioscience, biotechnology, and biochemistry》2013,77(9):1493-1503
In our study, it has been detected in vivo and in vitro that GSPE reversed high glucose-induced the increase of ICAM-1 and VCAM-1. It is shown that by western blotting detection, GSPE significantly inhibited the activation of NF-κB induced by high glucose while there was significant decrease of the expression of PKC with GSPE intervention. By adding the NF-κB blocker PDTC and the PKC inhibitor peptide 19–31(10?6 M), no significant difference was found in the levels of VCAM-1 and ICAM-1 among GSPE group, the PKC inhibitor peptide 19–31-added GSPE group and the PDTC-added GSPE group. So the conclusion could be drawn that PKC inhibition must be involved in GSPE decreasing the level of ICAM-1 and VCAM-1.We proved for the first time that GSPE prevented high glucose-induced the increase of ICAM-1 and VCAM-1 by PKC and NF-κB inhibition. These findings show a novel mechanism of the action GSPE preventing endothelial dysfunction, which may have clinical application values. 相似文献
138.
Bhupinder Pal Toula Bouras Wei Shi François Vaillant Julie M. Sheridan Naiyang Fu Kelsey Breslin Kun Jiang Matthew E. Ritchie Matthew Young Geoffrey J. Lindeman Gordon K. Smyth Jane E. Visvader 《Cell reports》2013,3(2):411-426
Highlights? The mammary epigenome is highly sensitive to steroid hormones at specific developmental stages ? Ezh2 links hormonal cues to changes in chromatin structure and gene expression ? Progesterone is a key in vivo regulator of Ezh2 ? Hormone-induced chromatin changes likely play a role in the initiation of breast cancer 相似文献
139.
140.
Xiao Wei Xin Chen Xia Wang Weiwei Zheng Dong Zhang Dajun Tian Songhui Jiang Choon Nam Ong Gengsheng He Weidong Qu 《PloS one》2013,8(3)
Drinking water chlorination plays a pivotal role in preventing pathogen contamination against water-borne disease. However, chemical disinfection leads to the formation of halogenated disinfection by products (DBPs). Many DBPs are highly toxic and are of health concern. In this study, we conducted a comprehensive measurements of DBPs, including iodoacetic acid (IAA), iodoform (IF), nine haloacetic acids and four trihalomethanes in drinking waters from 13 water plants in Shanghai, China. The results suggested that IAA and IF were found in all the water treatment plants, with maximum levels of 1.66 µg/L and 1.25 µg/L for IAA and IF, respectively. Owing to deterioration of water quality, the Huangpu River has higher IAA and IF than the Yangtze River. Our results also demonstrated that low pH, high natural organic matter, ammonia nitrogen, and iodide in source waters increased IAA and IF formation. Compared to chlorine, chloramines resulted in higher concentration of iodinated DBP, but reduced the levels of trihalomethanes. This is the first study to reveal the widespread occurrence of IAA and IF in drinking water in China. The data provide a better understanding on the formation of iodinated disinfection byproducts and the findings should be useful for treatment process improvement and disinfection byproducts controls. 相似文献