全文获取类型
收费全文 | 1571篇 |
免费 | 88篇 |
出版年
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 7篇 |
2018年 | 13篇 |
2017年 | 13篇 |
2016年 | 25篇 |
2015年 | 39篇 |
2014年 | 43篇 |
2013年 | 101篇 |
2012年 | 90篇 |
2011年 | 67篇 |
2010年 | 54篇 |
2009年 | 32篇 |
2008年 | 73篇 |
2007年 | 76篇 |
2006年 | 78篇 |
2005年 | 90篇 |
2004年 | 90篇 |
2003年 | 85篇 |
2002年 | 113篇 |
2001年 | 50篇 |
2000年 | 47篇 |
1999年 | 40篇 |
1998年 | 20篇 |
1997年 | 27篇 |
1996年 | 15篇 |
1995年 | 12篇 |
1994年 | 17篇 |
1993年 | 17篇 |
1992年 | 21篇 |
1991年 | 17篇 |
1990年 | 11篇 |
1989年 | 16篇 |
1988年 | 13篇 |
1987年 | 22篇 |
1986年 | 20篇 |
1985年 | 18篇 |
1984年 | 14篇 |
1983年 | 18篇 |
1982年 | 14篇 |
1981年 | 10篇 |
1980年 | 16篇 |
1979年 | 13篇 |
1978年 | 13篇 |
1977年 | 10篇 |
1976年 | 13篇 |
1974年 | 5篇 |
1973年 | 5篇 |
1970年 | 5篇 |
1969年 | 7篇 |
排序方式: 共有1659条查询结果,搜索用时 15 毫秒
101.
Ochiai H Ohtani T Ishida A Kusumi K Kato M Kohno H Kishikawa K Obata T Nakai H Toda M 《Bioorganic & medicinal chemistry letters》2004,14(1):207-210
Based on the hypothesis that the dose-limiting side effects of PDE4 inhibitors could be mediated via the central nervous system (CNS), design and synthesis of a hydrophilic analogue is considered to be one approach to improving the side-effect profile of Ariflo 1. Water-soluble piperidine derivatives were found to possess therapeutic potential. 相似文献
102.
Qing G Ma LC Khorchid A Swapna GV Mal TK Takayama MM Xia B Phadtare S Ke H Acton T Montelione GT Ikura M Inouye M 《Nature biotechnology》2004,22(7):877-882
Overexpression of proteins in Escherichia coli at low temperature improves their solubility and stability. Here, we apply the unique features of the cspA gene to develop a series of expression vectors, termed pCold vectors, that drive the high expression of cloned genes upon induction by cold-shock. Several proteins were produced with very high yields, including E. coli EnvZ ATP-binding domain (EnvZ-B) and Xenopus laevis calmodulin (CaM). The pCold vector system can also be used to selectively enrich target proteins with isotopes to study their properties in cell lysates using NMR spectroscopy. We have cloned 38 genes from a range of prokaryotic and eukaryotic organisms into both pCold and pET14 (ref. 3) systems, and found that pCold vectors are highly complementary to the widely used pET vectors. 相似文献
103.
104.
Xue Y Hieda Y Kimura K Takayama K Fujihara J Tsujino Y 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,811(1):53-58
Kinetic characteristics and toxic effects of benzalkonium chloride (BZK) following injection via jugular vein (JV), femoral artery (FA) and oral administration (PO) were experimentally investigated using rats. The BZK concentrations in blood and tissues (lung, liver and kidney) were determined by high-performance liquid chromatography with solid phase extraction. Toxic doses of 15 and 250 mg/kg of BZK were used for intravascular (JV and FA) and PO administration, respectively. The fatal effects appeared soon after the dose in JV-rats, while delayed in FA- or PO-rats. The blood BZK concentrations and the elimination half-lives were similar between JV- and FA-rats, while the distribution of BZK in tissues was slightly different. In PO administration, the rats that aspirated BZK into their lungs had some symptoms, while the rats that did not aspirate BZK appeared to be normal. The BZK concentrations in blood and tissues were significantly higher in the aspirated PO-rats. The toxic degree of BZK was correlated with the BZK concentration in orally dosed rats. Lung and kidney had higher BZK concentrations compared to blood or liver, and they could be the target organs of BZK.Keyword: Benzalkonium chloride 相似文献
105.
BACKGROUND: We examined gender difference in QTc interval distribution and its related factors in people with mental disorders. METHODS: We retrospectively reviewed medical charts of patients discharged from a university psychiatric unit between November 1997 and December 2000. Subjects were 328 patients (145 males and 183 females) taking psychotropics at their admission. We examined patient characteristics, medical history, diagnosis, and medication before admission. RESULTS: Mean QTc interval was 0.408 (SD = 0.036). QTc intervals in females were significantly longer than those in males. QTc of females without comorbidity was significantly longer than that of males. CONCLUSION: The influence of gender difference on QTc prolongation in people with mental disorders merits further research. 相似文献
106.
Ochiai H Ohtani T Ishida A Kusumi K Kato M Kohno H Odagaki Y Kishikawa K Yamamoto S Takeda H Obata T Nakai H Toda M 《Bioorganic & medicinal chemistry》2004,12(17):4645-4665
The hypothesis that the dose-limiting side effects of PDE4 inhibitors could be mediated via the central nervous system prompted us to design and synthesize a hydrophilic piperidine analog to improve the side effect profile of Ariflo 1, which is an orally active second-generation PDE4 inhibitor. During evaluation of various water-soluble piperidine analogs, 2a-b, 11b-14b, and 17a showed therapeutic potential in cross-species comparison studies. The following three findings were obtained: (1) The hydroxamic acid group, a well known metal chelator, caused a marked increase of inhibitory activity. (2) Water-soluble piperidine analogs lacked the configurational isomerism of Ariflo 1 without loss of inhibitory activity. (3) Replacement of the 4-methoxy residue with a difluoromethoxy residue led to an increase of in vivo potency. Structure-activity relationships are presented. Single-dose rat pharmacokinetic data for 11b, 12b, and 17a are also presented. 相似文献
107.
Assembly of initiation factors on individual replication origins at onset of S phase is crucial for regulation of replication timing and repression of initiation by S-phase checkpoint control. We dissected the process of preinitiation complex formation using a point mutation in fission yeast nda4-108/mcm5 that shows tight genetic interactions with sna41(+)/cdc45(+). The mutation does not affect loading of MCM complex onto origins, but impairs Cdc45-loading, presumably because of a defect in interaction of MCM with Cdc45. In the mcm5 mutant, however, Sld3, which is required for Cdc45-loading, proficiently associates with origins. Origin-association of Sld3 without Cdc45 is also observed in the sna41/cdc45 mutant. These results suggest that Sld3-loading is independent of Cdc45-loading, which is different from those observed in budding yeast. Interestingly, returning the arrested mcm5 cells to the permissive temperature results in immediate loading of Cdc45 to the origin and resumption of DNA replication. These results suggest that the complex containing MCM and Sld3 is an intermediate for initiation of DNA replication in fission yeast. 相似文献
108.
109.
Kai M Kaito C Fukamachi H Higo T Takayama E Hara H Ohya Y Igarashi K Shiokawa K 《Cell research》2003,13(3):147-158
In Xenopus, injection of S-adenosylmethionine decarboxylase (SAMDC) mRNA into fertilized eggs or 2-cell stage embryos induces massive cell dissociation and embryo-lysis at the early gastrula stage due toactivation of the maternal program of apoptosis. We injected SAMDC mRNA into only one of the animalside blastomeres of embryos at different stages of cleavage, and examined the timing of the onset of theapoptotic reaction. In the injection at 4-and 8-cell stages, a considerable number of embryos developed intotadpoles and in the injection at 16-and 32-cell stages, all the embryos became tadpoles, although tadpolesobtained were sometimes abnormal. However, using GFP as a lineage tracer, we found that descendant cellsof the blastomere injected with SAMDC mRNA at 8-to 32-cell stages are confined within the blastocoel atthe early gastrula stage and undergo apoptotic cell death within the blastocoel, in spite of the continued development of the injected embryos. These results indicate that cells overexpressed with SAMDC undergo apoptotic cell death consistently at the early gastrula stage, irrespective of the timing of the mRNA injection.We assume that apoptosis is executed in Xenopus early gastrulae as a “fall-safe“ mechanism to eliminate physiologically-severely damaged cells to save the rest of the embryo. 相似文献
110.
Oka S Tsuchie A Tokumura A Muramatsu M Suhara Y Takayama H Waku K Sugiura T 《Journal of neurochemistry》2003,85(6):1374-1381
2-Eicosa-5',8',11',14'-tetraenylglycerol (2-AG ether, HU310, noladin ether) is a metabolically stable ether-linked analogue of 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid receptor ligand. 2-AG ether has been used as a valuable experimental tool by a number of investigators. Recently, several groups reported that 2-AG ether is present in mammalian brains. We examined in detail whether 2-AG ether actually exists in the brains of various mammalian species. We found that 2-AG ether is not present, at least in an appreciable amount, in the rat brain by gas chromatography-mass spectrometry analysis and fluorometric high performance liquid chromatography analysis. The level of 2-AG ether in the rat brain was below 0.2 pmol/g brain, if at all present. Similar results were obtained for the mouse brain, hamster brain, guinea-pig brain and pig brain. The fact that 2-AG ether was not detected in the brains of various mammalian species is consistent with the fact that an ether bond is formed through enzymatic replacement of the fatty acyl moiety of 1-acyl dihydroxyacetone phosphate by a fatty alcohol, the resultant 1-O-alkyl dihydroxyacetone phosphate being a common intermediate of the biosynthesis of ether-linked lipids in mammalian tissues. It is rather questionable whether 2-AG ether is present in appreciable amounts in the brain and acts as an 'endogenous' cannabinoid receptor ligand. 相似文献