全文获取类型
收费全文 | 2206篇 |
免费 | 138篇 |
出版年
2022年 | 6篇 |
2021年 | 11篇 |
2020年 | 15篇 |
2019年 | 20篇 |
2018年 | 23篇 |
2017年 | 15篇 |
2016年 | 38篇 |
2015年 | 47篇 |
2014年 | 60篇 |
2013年 | 176篇 |
2012年 | 134篇 |
2011年 | 119篇 |
2010年 | 88篇 |
2009年 | 83篇 |
2008年 | 146篇 |
2007年 | 152篇 |
2006年 | 144篇 |
2005年 | 130篇 |
2004年 | 158篇 |
2003年 | 144篇 |
2002年 | 142篇 |
2001年 | 22篇 |
2000年 | 12篇 |
1999年 | 30篇 |
1998年 | 36篇 |
1997年 | 35篇 |
1996年 | 22篇 |
1995年 | 28篇 |
1994年 | 18篇 |
1993年 | 24篇 |
1992年 | 25篇 |
1991年 | 30篇 |
1990年 | 29篇 |
1989年 | 19篇 |
1988年 | 20篇 |
1987年 | 11篇 |
1986年 | 14篇 |
1985年 | 13篇 |
1984年 | 23篇 |
1983年 | 10篇 |
1982年 | 11篇 |
1981年 | 10篇 |
1980年 | 9篇 |
1979年 | 6篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1974年 | 3篇 |
1973年 | 6篇 |
1972年 | 3篇 |
排序方式: 共有2344条查询结果,搜索用时 15 毫秒
101.
Role of follicular dendritic cells in the early HIV-1 infection: in vitro model without specific antibody 总被引:2,自引:0,他引:2
Taruishi M Terashima K Dewan Z Yamamoto N Ikeda S Kobayashi D Eishi Y Yamazaki M Furusaka T Sugimoto M Ishii M Kitamura K Yamamoto N 《Microbiology and immunology》2004,48(9):693-702
About 90% of HIV-1 RNA in the lymph nodes is reported to localize in follicular dendritic cellsnetwork (FDC-NW) as early as several days after infection and as much as that in the late stage. But the mechanism remains to be fully understood. To elucidate the role of follicular dendritic cells (FDC) in the early stage of HIV-1 infection, FDC-like cell strains (FDCLC) were established and they were characterized in the co-culture system with T cells for their effect on HIV-1 trapping and replication in p24 immunoassay, immunohistochemistry as well as confocal and electronmicroscopy. Established FDCLC were positive for CNA-42, S-100alpha and intercellular desmosome-like junctions. L-SIGN and DC-SIGN were also detected in FDCLC. Alu-HIV-1 PCR analysis showed no HIV-1 integration in FDCLC. FDCLC trapped HIV-1 and transferred them to uninfected MOLT-4 T cells (MOLT-4) efficiently in the absence of specific antibody. FDCLC also accelerated HIV-1 replication in HIV-1-pre-exposed MOLT-4. These unique FDCLC effects were explained, at least partly, by the fact that FDCLC up-regulated CD4 expression in MOLT-4 and helped T cells escape from apoptosis in the co-culture. These data suggest that FDC/FDCLC engage not only in trapping but also in active expansion of HIV-1 in the absence of specific antibody. 相似文献
102.
Ohtaki H Dohi K Yofu S Nakamachi T Kudo Y Endo S Aruga T Goto N Watanabe J Kikuyama S Shioda S 《Regulatory peptides》2004,123(1-3):61-67
It has been reported that pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in preventing neuronal cell death and is also a potent vasodilator. Cerebral hypotension and hypoperfusion during cerebral ischemia and neurodegenerative diseases are well known as some of the negative factors which aggravate neuronal cell death. Nevertheless, the effect of PACAP on the cerebral circulation was not understood well. Therefore, in the present study, we determined the mean arterial blood pressure (MBP), regional cerebral blood flow (rCBF) and cerebral oxygen content (pO2) in mice, and estimated the therapeutically useful doses of PACAP. Under barbiturate anesthesia, polyethylene tubes were inserted into mice to monitor MBP and to administer PACAP (5 x 10(-13)-5 x 10(-8) mol/kg) or vasoactive intestinal peptide (VIP; 5 x 10(-12) and 5 x 10(-9) mol/kg). Then, MBP, rCBF and cerebral pO2 were simultaneously measured in the mice. PACAP (5 x 10(-10)-5 x 10(-9) mol/kg) injections transiently decreased MBP, and cerebral pO2. PACAP (5 x 10(-8) mol/kg) injections produced a long-lasting potent decline of MBP, rCBF and cerebral pO2. Therefore, PACAP should be applied at low doses which do not influence the MBP and cerebral circulation to determine the therapeutically useful doses of PACAP for neuroprotection. 相似文献
103.
104.
Komatsu M Chiba T Tatsumi K Iemura S Tanida I Okazaki N Ueno T Kominami E Natsume T Tanaka K 《The EMBO journal》2004,23(9):1977-1986
Several studies have addressed the importance of various ubiquitin-like (UBL) post-translational modifiers. These UBLs are covalently linked to most, if not all, target protein(s) through an enzymatic cascade analogous to ubiquitylation, consisting of E1 (activating), E2 (conjugating), and E3 (ligating) enzymes. In this report, we describe the identification of a novel ubiquitin-fold modifier 1 (Ufm1) with a molecular mass of 9.1 kDa, displaying apparently similar tertiary structure, although lacking obvious sequence identity, to ubiquitin. Ufm1 is first cleaved at the C-terminus to expose its conserved Gly residue. This Gly residue is essential for its subsequent conjugating reactions. The C-terminally processed Ufm1 is activated by a novel E1-like enzyme, Uba5, by forming a high-energy thioester bond. Activated Ufm1 is then transferred to its cognate E2-like enzyme, Ufc1, in a similar thioester linkage. Ufm1 forms several complexes in HEK293 cells and mouse tissues, revealing that it conjugates to the target proteins. Ufm1, Uba5, and Ufc1 are all conserved in metazoa and plants but not in yeast, suggesting its potential roles in various multicellular organisms. 相似文献
105.
106.
Abe S Chamnan C Miyamoto K Minamino Y Nouda M 《Marine biotechnology (New York, N.Y.)》2004,6(6):527-540
107.
Syntheses and biological evaluation of novel quinuclidine derivatives as squalene synthase inhibitors 总被引:2,自引:0,他引:2
Ishihara T Kakuta H Moritani H Ugawa T Sakamoto S Tsukamoto S Yanagisawa I 《Bioorganic & medicinal chemistry》2003,11(11):2403-2414
Squalene synthase (E.C. 2.5.1.21) catalyses the reductive dimerization of two molecules of farnesyl diphosphate to form squalene and is involved in the first committed step in cholesterol biosynthesis. Inhibition of this enzyme is therefore an attractive target for hypocholesterolemic strategies. A series of quinuclidine derivatives incorporating a tricyclic system was synthesized and evaluated for their ability to inhibit squalene synthase in vitro. A 9H-fluorene moiety was found to be optimal as the tricyclic system for potent inhibitory activity. Improved activity can be achieved with a conformationally constrained three-atom linkage connecting the tricyclic system with the quinuclidine nucleus. Among these compounds, (Z)-3-[2-(9H-fluoren-2-yloxy)ethylidene]-quinuclidine hydrochloride 31 was found to be a potent inhibitor of squalene synthase derived from hamster liver and human hepatoma cells with IC(50) values of 76 and 48 nM, respectively. Oral dosing of compound 31 demonstrated effective reduction of plasma non-HDL cholesterol levels in hamsters. 相似文献
108.
Unpaired structures in SCA10 (ATTCT)n.(AGAAT)n repeats 总被引:4,自引:0,他引:4
Potaman VN Bissler JJ Hashem VI Oussatcheva EA Lu L Shlyakhtenko LS Lyubchenko YL Matsuura T Ashizawa T Leffak M Benham CJ Sinden RR 《Journal of molecular biology》2003,326(4):1095-1111
A number of human hereditary diseases have been associated with the instability of DNA repeats in the genome. Recently, spinocerebellar ataxia type 10 has been associated with expansion of the pentanucleotide repeat (ATTCT)(n).(AGAAT)(n) from a normal range of ten to 22 to as many as 4500 copies. The structural properties of this repeat cloned in circular plasmids were studied by a variety of methods. Two-dimensional gel electrophoresis and atomic force microscopy detected local DNA unpairing in supercoiled plasmids. Chemical probing analysis indicated that, at moderate superhelical densities, the (ATTCT)(n).(AGAAT)(n) repeat forms an unpaired region, which further extends into adjacent A+T-rich flanking sequences at higher superhelical densities. The superhelical energy required to initiate duplex unpairing is essentially length-independent from eight to 46 repeats. In plasmids containing five repeats, minimal unpairing of (ATTCT)(5).(AGAAT)(5) occurred while 2D gel analysis and chemical probing indicate greater unpairing in A+T-rich sequences in other regions of the plasmid. The observed experimental results are consistent with a statistical mechanical, computational analysis of these supercoiled plasmids. For plasmids containing 29 repeats, which is just above the normal human size range, flanked by an A+T-rich sequence, atomic force microscopy detected the formation of a locally condensed structure at high superhelical densities. However, even at high superhelical densities, DNA strands within the presumably compact A+T-rich region were accessible to small chemicals and oligonucleotide hybridization. Thus, DNA strands in this "collapsed structure" remain unpaired and accessible for interaction with other molecules. The unpaired DNA structure functioned as an aberrant replication origin, in that it supported complete plasmid replication in a HeLa cell extract. A model is proposed in which unscheduled or aberrant DNA replication is a critical step in the expansion mutation. 相似文献
109.
Brain-derived neurotrophic factor shows a protective effect and improves recovery of the ERG b-wave response in light-damage 总被引:3,自引:0,他引:3
We investigated the neuroprotective effects of brain-derived neurotrophic factor (BDNF) and its influence on the functional recovery of the retina following light-induced retinal damage by electroretinogram (ERG). Rats were exposed to constant fluorescent light for 2, 5, 7, or 14 days, then returned to a cyclic light environment for 14 days. The result indicated that BDNF had few effects on the a-wave amplitude, but there was a statistically significant difference in the b-wave amplitudes between BDNF-treated and control eyes from day 0-14 of the recovery period following 2 days of light exposure (p < 0.05). Our findings suggest that BDNF not only protects the retinal neuronal function but also enhances the recovery from retinal light damage. 相似文献
110.