全文获取类型
收费全文 | 37814篇 |
免费 | 1650篇 |
国内免费 | 1164篇 |
出版年
2024年 | 25篇 |
2023年 | 379篇 |
2022年 | 597篇 |
2021年 | 841篇 |
2020年 | 823篇 |
2019年 | 1262篇 |
2018年 | 1241篇 |
2017年 | 686篇 |
2016年 | 849篇 |
2015年 | 1125篇 |
2014年 | 2127篇 |
2013年 | 2645篇 |
2012年 | 1394篇 |
2011年 | 2213篇 |
2010年 | 1589篇 |
2009年 | 1804篇 |
2008年 | 1992篇 |
2007年 | 2112篇 |
2006年 | 1961篇 |
2005年 | 1775篇 |
2004年 | 1561篇 |
2003年 | 1374篇 |
2002年 | 1285篇 |
2001年 | 832篇 |
2000年 | 749篇 |
1999年 | 753篇 |
1998年 | 818篇 |
1997年 | 673篇 |
1996年 | 579篇 |
1995年 | 597篇 |
1994年 | 521篇 |
1993年 | 407篇 |
1992年 | 374篇 |
1991年 | 308篇 |
1990年 | 265篇 |
1989年 | 233篇 |
1988年 | 211篇 |
1987年 | 203篇 |
1986年 | 148篇 |
1985年 | 193篇 |
1984年 | 251篇 |
1983年 | 198篇 |
1982年 | 180篇 |
1981年 | 129篇 |
1980年 | 114篇 |
1979年 | 79篇 |
1978年 | 41篇 |
1977年 | 33篇 |
1976年 | 20篇 |
1974年 | 18篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
11.
《Cell reports》2020,30(4):1052-1062.e5
- Download : Download high-res image (154KB)
- Download : Download full-size image
12.
13.
Ahmed Hasbi Jocelyne Polastron Stéphane Allouche Laura Stanasila Dominique Massotte Philippe Jauzac 《Journal of neurochemistry》1998,70(5):2129-2138
Abstract: Phosphorylation of G protein-coupled receptors is considered an important step during their desensitization. In SK-N-BE cells, recently presented as a pertinent model for the studies of the human δ-opioid receptor, pretreatment with the opioid agonist etorphine increased time-dependently the rate of phosphorylation of a 51-kDa membrane protein. Immunological characterization of this protein with an antibody, raised against the amino-terminal region of the cloned human δ-opioid receptor, revealed that it corresponded to the δ-opioid receptor. During prolonged treatment with etorphine, phosphorylation increased as early as 15 min to reach a maximum within 1 h. Phosphorylation and desensitization of adenylyl cyclase inhibition paralleled closely and okadaic acid inhibited the resensitization, a result strongly suggesting that phosphorylation of the δ-opioid receptor plays a prominent role in its rapid desensitization. The increase in phosphorylation of the δ-opioid receptor, as well as its desensitization, was not affected by H7, an inhibitor of protein kinase A and protein kinase C, but was drastically reduced by heparin or Zn2+ , known to act as G protein-coupled receptor kinase (GRK) inhibitors. These results are the first to show, on endogenously expressed human δ-opioid receptor, that a close link exists between receptor phosphorylation and agonist-promoted desensitization and that desensitization involves a GRK. 相似文献
14.
《Journal of molecular biology》2021,433(21):167224
Retinoblastoma-binding protein 1 (RBBP1) is involved in gene regulation, epigenetic regulation, and disease processes. RBBP1 contains five domains with DNA-binding or histone-binding activities, but how RBBP1 specifically recognizes chromatin is still unknown. An AT-rich interaction domain (ARID) in RBBP1 was proposed to be the key region for DNA-binding and gene suppression. Here, we first determined the solution structure of a tandem PWWP-ARID domain mutant of RBBP1 after deletion of a long flexible acidic loop L12 in the ARID domain. NMR titration results indicated that the ARID domain interacts with DNA with no GC- or AT-rich preference. Surprisingly, we found that the loop L12 binds to the DNA-binding region of the ARID domain as a DNA mimic and inhibits DNA binding. The loop L12 can also bind weakly to the Tudor and chromobarrel domains of RBBP1, but binds more strongly to the DNA-binding region of the histone H2A-H2B heterodimer. Furthermore, both the loop L12 and DNA can enhance the binding of the chromobarrel domain to H3K4me3 and H4K20me3. Based on these results, we propose a model of chromatin recognition by RBBP1, which highlights the unexpected multiple key roles of the disordered acidic loop L12 in the specific binding of RBBP1 to chromatin. 相似文献
15.
Selective increase in cytokeratin synthesis in cultured rat hepatocytes in response to hormonal stimulation 总被引:3,自引:0,他引:3
I Leroux-Nicollet M Noel H Baribault R Goyette N Marceau 《Biochemical and biophysical research communications》1983,114(2):556-563
Addition of a combination of insulin, dexamethasone and EGF at seeding time to cultured rat hepatocytes in serum-free medium caused a selective increase in the biosynthesis of particular cytokeratin components. This increase was prominent during the first day in culture. No significant increases were detected in the absence of hormones or in the presence of either hormones added alone or in pairs, except in the case of insulin plus dexamethasone, which yielded an effect close to that obtained with the three factors. Interestingly, the latter condition also maintained a high level of albumin production over a 6-day period in culture. 相似文献
16.
Masaru Kubota Ying-Wei Lin Keigo Hamahata Machiko Sawada Seiji Koishi Haruyo Hirota Yoshihiro Wakazono 《Mutation Research - Genetic Toxicology and Environmental Mutagenesis》2000,470(2):21
The occurrence of a second neoplasm is one of the major obstacles in cancer chemotherapy. The elucidation of the genotoxic effects induced by anti-cancer drugs is considered to be helpful in identifying the degree of cancer risk. Numerous investigations on cancer patients after chemotherapy have demonstrated: (i) an increase in the in vivo somatic cell mutant frequency (Mf) at three genetic loci, including hypoxanthine–guanine phosphoribosyl-transferase (hprt), glycophorin A (GPA), and the T-cell receptor (TCR), and (ii) alterations in the mutational spectra of hprt mutants. However, the time required for and the degree of such changes are quite variable among patients even if they have received the same chemotherapy, suggesting the existence of underlying genetic factor(s). Accordingly, some cancer patients prior to chemotherapy as well as patients with cancer-prone syndrome have been found to show an elevated Mf. Based on the information obtained from somatic cell mutation assays, an individualized chemotherapy should be considered in order to minimize the risk of a second neoplasm. 相似文献
17.
Interleukin (IL)-6, a cytokine featuring redundancy and pleiotropic activity, contributes to host defense against acute environmental stress, while dysregulated persistent IL-6 production has been demonstrated to play a pathological role in various autoimmune and chronic inflammatory diseases. Targeting IL-6 is thus a rational approach to the treatment of these diseases. Indeed, clinical trials of tocilizumab, a humanized anti-IL-6 receptor antibody have verified its efficacy and tolerable safety for patients with rheumatoid arthritis, Castleman''s disease and systemic juvenile idiopathic arthritis, resulting in approval of this innovative biologic for treatment of these diseases. Moreover, a considerable number of case reports and pilot studies of off-label use of tocilizumab point to the beneficial effects of tocilizumab for a variety of other phenotypically different autoimmune and chronic inflammatory diseases. Elucidation of the source of IL-6 and of mechanisms through which IL-6 production is dysregulated can thus be expected to lead to clarification of the pathogenesis of various diseases. 相似文献
18.
Low-angle laser-light scattering (LALLS) was employed to measure the absolute molecular weight of chicken liver NAD+ kinase (NADK). The weight-average molecular weight (Mw) was found to be 275 000 +/- 15 000. The corresponding value for the second virial coefficient was -1.65 X 10(-3) ml X mol X g2. The value for Mw is in close accord with estimates reported for pigeon liver (270 000) and C. utilis (260 000) NADK. If the active enzyme is a dimer, the weight difference between pigeon/chicken liver and rabbit liver (136 000) NADK would indicate that the latter enzyme is an active monomer unit. 相似文献
19.
20.
《Cell reports》2020,30(3):739-754.e4
- Download : Download high-res image (99KB)
- Download : Download full-size image