全文获取类型
收费全文 | 3672篇 |
免费 | 253篇 |
国内免费 | 5篇 |
专业分类
3930篇 |
出版年
2023年 | 13篇 |
2022年 | 23篇 |
2021年 | 54篇 |
2020年 | 21篇 |
2019年 | 47篇 |
2018年 | 50篇 |
2017年 | 56篇 |
2016年 | 87篇 |
2015年 | 126篇 |
2014年 | 150篇 |
2013年 | 253篇 |
2012年 | 243篇 |
2011年 | 267篇 |
2010年 | 129篇 |
2009年 | 135篇 |
2008年 | 261篇 |
2007年 | 234篇 |
2006年 | 248篇 |
2005年 | 255篇 |
2004年 | 253篇 |
2003年 | 217篇 |
2002年 | 189篇 |
2001年 | 31篇 |
2000年 | 19篇 |
1999年 | 40篇 |
1998年 | 53篇 |
1997年 | 36篇 |
1996年 | 38篇 |
1995年 | 35篇 |
1994年 | 41篇 |
1993年 | 35篇 |
1992年 | 21篇 |
1991年 | 17篇 |
1990年 | 21篇 |
1989年 | 27篇 |
1988年 | 12篇 |
1987年 | 14篇 |
1986年 | 14篇 |
1985年 | 31篇 |
1984年 | 23篇 |
1983年 | 17篇 |
1982年 | 16篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1978年 | 11篇 |
1977年 | 5篇 |
1976年 | 9篇 |
1975年 | 4篇 |
1974年 | 6篇 |
1967年 | 3篇 |
排序方式: 共有3930条查询结果,搜索用时 15 毫秒
991.
The participation of cAMP in photosignal transduction in cyanobacteria was investigated. When cells of the cyanobacterium Synechocystis sp. PCC 6803 were exposed to light, cellular cAMP contents increased within a few minutes. Among incident monochromatic lights, blue light (450 nm) markedly increased cellular cAMP content, while red (630 nm) and far-red (720 nm) lights did not. Disruption of the cya1 gene encoding an adenylate cyclase caused the insensitivity of cellular cAMP level to blue light. Treatment of wild-type cells with the flavin antagonist phenylacetic acid inhibited this blue light effect. The motility of wild-type cells was enhanced by blue light, whereas that of cya1 mutant cells was not. Based on these results, we concluded that a blue light-cAMP signal transduction system stimulates the motility of Synechocystis sp. PCC 6803. 相似文献
992.
Xu Y Tanaka M Arai H Aoki J Prestwich GD 《Bioorganic & medicinal chemistry letters》2004,14(21):5323-5328
We describe an efficient method for the synthesis of alkyl lysophosphatidic acid (LPA) analogs as well as alkyl LPA mono- and difluoromethylene phosphonate analogs. Each alkyl LPA analog was evaluated for subtype-specific LPA receptor agonist activity using a cell migration assay for LPA(1) activation in cancer cells and an intracellular calcium mobilization assay for LPA(2) and LPA(3) activation. Alkyl LPAs induced pronounced cell migration activity with equivalent or higher potency than sn-1-oleoyl LPA, while the alkyl LPA fluoromethylene phosphonates proved to be less potent agonists in this assay. However, each alkyl LPA analog activated Ca(2+) release by activation of LPA(2) and LPA(3) receptors. Interestingly, the absolute configuration of the sn-2 hydroxyl group of the alkyl LPA analogs was not recognized by any of the three LPA receptors. The use of alkyl LPA analogs further expands the scope of structure-activity studies, which will better define LPA-LPA receptor interactions. 相似文献
993.
994.
995.
Mori S Yamasaki M Maruyama Y Momma K Kawai S Hashimoto W Mikami B Murata K 《Biochemical and biophysical research communications》2005,327(2):500-508
NAD kinase is a key enzyme in NADP biosynthesis. We solved the crystal structure of polyphosphate/ATP-NAD kinase from Mycobacterium tuberculosis (Ppnk) complexed with NAD (Ppnk-NAD) at 2.6A resolution using apo-Ppnk structure solved in this work, and revealed the details of the structure and NAD-binding site. Superimposition of tertiary structures of apo-Ppnk and Ppnk-NAD demonstrated a substantial conformational difference in a loop (Ppnk-flexible loop). As a quaternary structure, these Ppnk structures exhibited tetramer as in solution condition. Notably, the Ppnk-flexible loop was involved in the intersubunit contact and probably related to the NAD-binding of the other subunit. Furthermore, the two residues (Asp189, His226) substantially contributed to creating NAD-binding site on the other subunit. The two residues and the residues involved in NAD-binding were conserved. However, residues corresponding to the Ppnk-flexible loop were not conserved, making us to speculate that the Ppnk-flexible loop may be Ppnk-specific. 相似文献
996.
Tomemori Y Ichiba M Kusumoto A Mizuno E Sato D Muroya S Nakamura M Kawaguchi H Yoshida H Ueno S Nakao K Nakamura K Aiba A Katsuki M Sano A 《Journal of neurochemistry》2005,92(4):759-766
Chorea-acanthocytosis (CHAC) is a hereditary neurodegenerative disorder with autosomal recessive transmission, in which selective degeneration of striatum has been reported in brain pathology. Clinically, CHAC shows Huntington's disease-like neuropsychiatric symptoms and red blood cell acanthocytosis. Recently, we identified the gene, CHAC, encoding a novel protein, chorein, in which a deletion mutation was found in Japanese families with CHAC. In the present study, we have identified the mouse CHAC cDNA sequence and the exon-intron structures of the gene and produced a CHAC model mouse introducing no. 60-61 exon deletion corresponding to a human disease mutation by a gene-targeting technique. The mice began to show acanthocytosis and motor disturbance in old age. In behavioral observations, locomotor activity was significantly decreased and the contact time at social interaction test was decreased significantly in the model mice. In the brain pathology, many apoptotic cells were observed in the striatum of the mutant mice. In neurochemical determinations, the dopamine metabolite, homovanillic acid, concentration decreased significantly in the portion including the midbrain of the mutant mice. These findings are consistent with the human results reported elsewhere and indicate that the CHAC model mice showed a mild phenotype with late adult onset. The CHAC model mouse therefore provides a good model system to study the human disease. 相似文献
997.
Suzuki N Nonaka H Tsuge Y Okayama S Inui M Yukawa H 《Applied microbiology and biotechnology》2005,69(2):151-161
A precise and scarless genome excision method, employing the Cre/loxP system in concert with double-strand break (DSB)-stimulated intramolecular recombination was developed. The DSBs were mediated by the restriction endonuclease, I-SceI. It permitted multiple deletions of independent 14-, 43-, and 10-kb-long genomic regions on the Corynebacterium glutamicum genome. Accuracy of deletion was confirmed by the loss of marker genes, PCR, and sequencing of new genome joints. Eleven, 58, and 4 genes were predicted on the 14-, 43-, and 10-kb deleted regions, respectively. Although the resultant mutant lost a total of 67 kb encoding 73 genes, it still exhibited normal growth under standard laboratory conditions. Such a large segment deletion method in which multiple, successive deletions are possible is useful for genome engineering. 相似文献
998.
Angiotensin III (Ang III) as well as angiotensin II (Ang II) suppressed body weight loss of the clam worm Perinereis sp. under a hyper-osmotic condition, and enhanced body weight gain under a hypo-osmotic condition. Under a drying condition where the water inflow from outside the body was eliminated, Ang II suppressed body weight loss, but Ang III did not. Under these conditions, angiotensins I, IV, and (1–7) had no effect, and saralasin blocked the effects of Ang II and Ang III. It is concluded that Ang II and Ang III upregulate body fluid volume of the clam worm via Ang II receptors in different ways. 相似文献
999.
Marine birnavirus (MABV) is a member of the genus Aquabirnavirus of the family Birnaviridae. MABV is an unenveloped icosahedral virus about 60 nm in diameter with two genomes of double-stranded RNA. MABV adsorbed not only onto the cell surfaces of susceptible (CHSE-214 and RSBK-2) cells but also onto resistant (FHM and EPC) cells. Furthermore, the virus entered into the cytoplasm through the endocytotic pathway in CHSE-214, RSBK-2 and FHM cells but did not penetrate EPC cells. The virus was found to bind to an around 250 kDa protein on CHSE-214, RSBK-2, FHM and EPC cells. The syntheses of viral proteins pVP2, NS and VP3 and further proteolytic processing after viral infection were examined by using Western blot analysis. pVP2, NS and VP3 were detected in the cytosolic fractions of CHSE-214, RSBK-2 and FHM cells at 4 h after infection. At this time, VP3 underwent further proteolytic processing in the cytosolic fractions of CHSE-214 and RSBK-2 cells. The expression of pVP2, NS and VP3 increased and pVP2 and NS also underwent further proteolytic processing similar to VP3 in the cytosolic fractions of CHSE-214, RSBK-2 and FHM cells at 8 h after infection. The further proteolytic processing of VP3 was detected in the nuclear fractions of CHSE-214, RSBK-2, but VP3 was detected as a single band in the nuclear fraction of FHM cells. pVP2 and NS were detected as thin bands only in the nuclear fractions of CHSE-214 cells. The results of Western blot analysis demonstrated that pVP2, NS and VP3 are localized in the nuclear fraction when they were independently expressed in CHSE-214, RSBK-2, FHM and EPC cells. The expression pattern in the cytosolic fraction was identical among the four cell lines when pVP2 and NS were independently expressed. However, pVP2 and NS were not detected in the nuclear fraction of CHSE-214 cells. Further proteolytic processing of VP3 was detected in both cytosolic and nuclear fractions of RSBK-2 ,FHM and EPC cells (Low level in EPC cell), but not in CHSE-214 cells when VP3 was independently expressed. Then, the processes of preVP2 to form morphological assemblages in the presence of VP3 or the cleavage of VP3 into two proteins in CHSE-214 cells were studied. When preVP2- and VP3 were co-expressed, virion like particles (64 nm, diameter) were observed close to the nuclear membrane by electron microscopy. The co-expression of preVP2 and the cleaved VP3 proteins led to an efficient assembly of tubules (22 nm, diameter). Further important finds will be obtained by this infection system using 4 fish cell lines in the next couple of years. 相似文献
1000.
Evolutionary conserved N-terminal domain of Nrf2 is essential for the Keap1-mediated degradation of the protein by proteasome 总被引:1,自引:0,他引:1
Katoh Y Iida K Kang MI Kobayashi A Mizukami M Tong KI McMahon M Hayes JD Itoh K Yamamoto M 《Archives of biochemistry and biophysics》2005,433(2):342-350
Under homeostatic conditions, Nrf2 activity is constitutively repressed. This process is dependent on Keap1, to which Nrf2 binds through the Neh2 domain. Since the N-terminal subdomain of Neh2 (Neh2-NT) contains evolutionarily conserved motifs, we examined the roles they play in the degradation of Nrf2. In Neh2-NT, we defined a novel motif that is distinct from the previously characterized DIDLID motif and designated it DLG motif. Deletion of Neh2-NT or mutation of the DLG motif largely abolished the Keap1-mediated degradation of Nrf2. These mutations were found to enfeeble the binding affinity of Nrf2 to Keap1. The Neh2-NT subdomain directed DLG-dependent, Keap1-independent, degradation of a reporter protein in the nucleus. By contrast, mutation of DLG did not affect the half-life of native Nrf2 protein in the nucleus under oxidative stress conditions. These results thus demonstrate that DLG motif plays essential roles in the Keap1-mediated proteasomal degradation of Nrf2 in the cytoplasm. 相似文献