全文获取类型
收费全文 | 20467篇 |
免费 | 1739篇 |
国内免费 | 1302篇 |
出版年
2024年 | 32篇 |
2023年 | 171篇 |
2022年 | 296篇 |
2021年 | 727篇 |
2020年 | 572篇 |
2019年 | 671篇 |
2018年 | 740篇 |
2017年 | 592篇 |
2016年 | 800篇 |
2015年 | 1236篇 |
2014年 | 1450篇 |
2013年 | 1516篇 |
2012年 | 1880篇 |
2011年 | 1833篇 |
2010年 | 1129篇 |
2009年 | 959篇 |
2008年 | 1276篇 |
2007年 | 1143篇 |
2006年 | 972篇 |
2005年 | 878篇 |
2004年 | 872篇 |
2003年 | 685篇 |
2002年 | 591篇 |
2001年 | 428篇 |
2000年 | 343篇 |
1999年 | 316篇 |
1998年 | 176篇 |
1997年 | 127篇 |
1996年 | 99篇 |
1995年 | 96篇 |
1994年 | 88篇 |
1993年 | 62篇 |
1992年 | 104篇 |
1991年 | 97篇 |
1990年 | 72篇 |
1989年 | 65篇 |
1988年 | 52篇 |
1987年 | 34篇 |
1986年 | 34篇 |
1985年 | 31篇 |
1984年 | 17篇 |
1983年 | 25篇 |
1982年 | 17篇 |
1981年 | 16篇 |
1980年 | 22篇 |
1979年 | 24篇 |
1978年 | 17篇 |
1977年 | 19篇 |
1975年 | 14篇 |
1974年 | 17篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
991.
Hong SY Chung KH You HJ Choi IH Chae MJ Han JY Jung OJ Kang SJ Ryu CK 《Bioorganic & medicinal chemistry letters》2004,14(13):3563-3566
A series of 6-arylamino-5-chloro-benzimidazole-4,7-diones were synthesized and tested for their inhibitory activity on the rat aortic smooth muscle cell (RAoSMC) proliferation. Among them, 6-arylamino-5-chloro-2-methyl-benzimidazole-4,7-diones exhibited potent antiproliferative activity. Benzimidazole-4,7-dione 2c activated SAPK/JNK signaling pathway in the RAoSMCs. 相似文献
992.
Synthesis and biological activity of new quinoxaline antibiotics of echinomycin analogues 总被引:5,自引:0,他引:5
Novel quinoxaline antibiotics having the methylenedithioether bridge as an analogue of echinomycin have been synthesized by insertion of methylene moiety between -S-S- bond. The compound 1a shows remarkable cytotoxicities against human tumor various cell lines, and is active VRE (vancomycin-resistant enterococci) within MIC range 0.5-8 microg/mL. According to the eukaryotic or prokaryotic data, 1a might be a first analogue to replace echinomycin. 相似文献
993.
Park HG Choi JY Choi SH Park MK Lee J Suh YG Cho H Oh U Lee J Kang SU Lee J Kim HD Park YH Su Jeong Y Kyu Choi J Jew SS 《Bioorganic & medicinal chemistry letters》2004,14(3):787-791
A series of N-4-substituted-benzyl-N'-tert-butylbenzyl thioureas were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor in rat DRG neurons. Their structure-activity relationship reveals that not only the two oxygens and amide hydrogen of sulfonamido group, but also the optimal size of methyl in methanesulfonamido group play an integral role for the antagonistic activity on vanilloid receptor. 相似文献
994.
Helal CJ Sanner MA Cooper CB Gant T Adam M Lucas JC Kang Z Kupchinsky S Ahlijanian MK Tate B Menniti FS Kelly K Peterson M 《Bioorganic & medicinal chemistry letters》2004,14(22):5521-5525
High-throughput screening with cyclin-dependent kinase 5 (cdk5)/p25 led to the discovery of N-(5-isopropyl-thiazol-2-yl)isobutyramide (1). This compound is an equipotent inhibitor of cdk5 and cyclin-dependent kinase 2 (cdk2)/cyclin E (IC(50)=ca. 320nM). Parallel and directed synthesis techniques were utilized to explore the SAR of this series. Up to 60-fold improvements in potency at cdk5 and 12-fold selectivity over cdk2 were achieved. 相似文献
995.
Zhu C Zhang Y Zhang YF Yi Li J Boado RJ Pardridge WM 《The journal of gene medicine》2004,6(8):906-912
BACKGROUND: The tissue-specific expression of an exogenous gene, under the influence of a tissue-specific promoter, has been examined in the past with pro-nuclear injections of the transgene and the development of transgenic mouse models. 'Adult transgenics' is possible with the acute expression of an exogenous gene that is administered to adult animals, providing the transgene can be effectively delivered to distant sites following an intravenous administration. METHODS: The organ specificity of exogenous gene expression in adult mice was examined with a bacterial beta-galactosidase (LacZ) expression plasmid under the influence of the bovine rhodopsin gene promoter. The 8-kb plasmid DNA was delivered to organs following an intravenous administration with the pegylated immunoliposome (PIL) non-viral gene transfer technology. The PIL carrying the gene was targeted to organs with the rat 8D3 monoclonal antibody (MAb) to the mouse transferrin receptor (TfR). RESULTS: The rhodopsin/beta-galactosidase gene was expressed widely in both the eye and the brain of adult mice, but was not expressed in peripheral tissues, including liver, spleen, lung, or heart. Ocular expression included the retinal-pigmented epithelium, the iris, and ciliary body, and brain expression was observed in neuronal structures throughout the cerebrum and cerebellum. CONCLUSIONS: The expression of trans-genes in adult animals is possible with the PIL non-viral gene transfer method. The opsin promoter enables tissue-specific gene expression in the eye, as well as the brain of adult mice, whereas gene expression in peripheral tissues, such as liver or spleen, is not observed. 相似文献
996.
Identification and characterization of a novel angiostatin-binding protein by the display cloning method 总被引:3,自引:0,他引:3
Angiostatin is a potent anti-angiogenic protein. To examine the angiostatin-interacting proteins, we used the display-cloning method with a T7 phage library presenting human cDNAs. The specific T7 phage clone that bound to the immobilized angiostatin was isolated, and a novel gene encoding the displayed polypeptide on the isolated T7 phage was identified. The displayed angiostatin-binding sequence was expressed in E. coli as a soluble protein and purified to homogeneity. This novel angiostatin-binding region interacted specifically to angiostatin with a dissociation constant of 3.4 x 10(-7) M. A sequence analysis showed that the identified sequence was a part of the large ORF of 1,998 amino acids, whose function has not yet been characterized. A Northern analysis indicated that the gene containing the angiostatin-binding sequence was expressed differentially in the developmental stages or cell types. 相似文献
997.
The activities of antioxidant enzymes in response to oxidative stresses and hormones in paraquat-tolerant Rehmannia glutinosa plants 总被引:1,自引:0,他引:1
Choi DG Yoo NH Yu CY de Los Reyes B Yun SJ 《Journal of biochemistry and molecular biology》2004,37(5):618-624
All members of R. glutinosa show the unique characteristic of intrinsic tolerance to paraquat (PQ). Antioxidant enzymes have been proposed to be the primary mechanism of PQ resistance in several plant species. Therefore, the antioxidant enzyme systems of R. glutinosa were evaluated by comparatively analyzing cellular antioxidant enzyme levels, and their responses of oxidative stresses and hormones. The levels of ascorbate peroxidase (APX), glutathione reductase (GR), non-specific peroxidase (POX), and superoxide dismutase (SOD) were 7.3-, 4.9-, 2.7- and 1.6-fold higher in PQ-tolerant R. glutinosa than in PQ-susceptible soybeans. However, the activity of catalase (CAT) was about 12-fold higher in the soybeans. The activities of antioxidant enzymes reduced after PQ treatment in the two species, with the exception of POX and SOD in R. glutinosa, which increased by about 40 %. Interestingly, the activities of APX, SOD and POX in R. glutinosa, relative to those in soybeans, were further increased by 49, 67 and 93 % after PQ treatment. The considerably higher intrinsic levels, and increases in the relative activities of antioxidant enzymes in R. glutinosa under oxidative stress support the possible role of these enzymes in the PQ tolerance of R. glutinosa. However, the relatively lower levels of SOD versus PQ tolerance, and the mixed responses of antioxidant enzymes to stresses and hormones, suggest a possible alternative mechanism(s) for PQ tolerance in R. glutinosa. 相似文献
998.
Kim SU Lee KM Park SK Yoo KY Noh DY Choe KJ Ahn SH Hirvonen A Kang D 《Journal of biochemistry and molecular biology》2004,37(5):582-585
To evaluate the potential association between the GSTP1 genotype and the development of breast cancer, a hospital based case-control study was conducted on Korean women. The study population consisted of 171 histologically confirmed incident breast cancer cases and 171 age-matched controls with no present or previous history of cancer. PCR-RFLP was used for the GSTP1 genotyping and statistical evaluations were performed using an unconditional logistic regression model. Postmenopausal women with the GSTP1 Val allele were found to have a reduced risk of breast cancer (OR = 0.3, 95 % CI = 0.10-0.74). A significant interaction was observed between the GSTP1 genotype and alcohol consumption (p for interaction = 0.01); compared with never-drinking women with Ile/Ile genotype, ever-drinking women with the GSTP1 Val allele had almost a three-fold risk of breast cancer (OR = 2.9, 95 % CI = 1.05-7.85), whereas never-drinking women with Val allele had half this risk (OR = 0.5, 95 % CI = 0.27-0.93). Our findings suggest that the GSTP1 polymorphism influences individual susceptibility to breast cancer in the Korean women and this effect may be modified by alcohol consumption. 相似文献
999.
Kim SH Lee DG Yoo JH Choi SM Choi JH Shin WS Lee K Yong D Lee WG Youn BS Kang MW 《Journal of microbiology (Seoul, Korea)》2004,42(2):143-146
Vancomycin-resistant Enterococcus faecium (VREFM) is becoming a threatening pathogen. We identified a gene called DD1.5K by differential display-PCR, which was preferentially expressed in the bloodstream isolates of VREFM. Due to its amino acid similarity to transfer complex protein, trsE, and tissue-specific expression, this gene may be involved in virulence of VREFM. 相似文献
1000.
Kim H Lee SJ Park JY Park YW Kim HS Kang HY Hur BK Ryu YW Han SI Kim JS 《Journal of microbiology (Seoul, Korea)》2004,42(1):25-31
Sf9 cells have obvious advantages for the conventional production technology of vaccine. They are useful tools for high concentration and large-scale cultures. Sf9 cells were grown to maximal concentration, 8 x 10(6) cells/ml in a 500ml spinner flask, with a doubling time at the exponentially growing phase of 24.5 hours, using serum-free media. To explore the ability of Sf9 cells to be infected by the Japanese encephalitis (JE) virus Beijing-1 strain, Sf9 cells were infected with the virus. By 4-5 days post-infection, 10-15% of the Sf9 cells showed cytopathic effect (CPE), from granularity to the formation of syncytia and multinucleated giant cells continuously observed over a period of 35 days. Positive fluorescent reactions were detected in 30-40% of cells infected with the JE virus Beijing-1 strain, and the uninfected Sf9 cells were completely negative. Virus particles, propagated in Sf9 and Vero cells, were concentrated by sedimentation on 40% trehalose cushions by ultracentrifugation, and showed identical patterns of viral morphogenesis. Complete virus particles, 40 to 50 nm in diameter, were observed, and JE virus envelope (E) proteins, at 53 kDa, were found in the western blot analysis to the anti-JE virus E protein monoclonal antibody and reacted as a magenta band in the same position to the glycoprotein staining. To evaluate whether the infectious virus was produced in Sf9 cells inoculated with the JE virus Beijing-1 stain, Sf9 cells were inoculated with the virus, and sample harvested every 5 days. The titers of the JE virus Beijing-1 strain rose from 1.0 x 10(5) to 1.5 x 10(6) pfu/ml. The infected Sf9 cells could be sub-cultured in serum-free medium, with no change in the plaque sizes formed by the JE virus Beijing-1 strain in the plaque assay. It is suggested that the ability of the JE virus Beijing-1 strain to infect Sf9 cells in serum-free media will provide a useful insect cell system, where the JE virus replication, cytopathogenicity and vaccine immunogen can be studied. 相似文献