全文获取类型
收费全文 | 2019篇 |
免费 | 134篇 |
出版年
2024年 | 3篇 |
2023年 | 15篇 |
2022年 | 48篇 |
2021年 | 68篇 |
2020年 | 58篇 |
2019年 | 62篇 |
2018年 | 78篇 |
2017年 | 68篇 |
2016年 | 85篇 |
2015年 | 145篇 |
2014年 | 133篇 |
2013年 | 147篇 |
2012年 | 144篇 |
2011年 | 133篇 |
2010年 | 100篇 |
2009年 | 79篇 |
2008年 | 123篇 |
2007年 | 95篇 |
2006年 | 83篇 |
2005年 | 57篇 |
2004年 | 63篇 |
2003年 | 53篇 |
2002年 | 74篇 |
2001年 | 41篇 |
2000年 | 29篇 |
1999年 | 28篇 |
1998年 | 17篇 |
1997年 | 13篇 |
1996年 | 9篇 |
1995年 | 7篇 |
1994年 | 13篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 12篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1967年 | 2篇 |
排序方式: 共有2153条查询结果,搜索用时 15 毫秒
131.
Vasconcelos SM Nascimento VS Nogueira CR Vieira CM Sousa FC Fonteles MM Viana GS 《Behavioural processes》2003,63(1):45-52
The present work shows the effects of a typical neuroleptic drug (haloperidol, HAL) on rat behavior (catalepsy and locomotor activity) and dopaminergic D2-like receptor densities in the hippocampus and striatum. Male Wistar rats (2-3 months old) were treated daily for 30 days with HAL (0.2 or 1mg/kg, intraperitoneally (i.p.)). At the end of treatment and 1h or 1, 3, 7 and 15 days after drug withdrawal, animals were subjected to behavioral tests and sacrificed afterwards for binding assays. The results showed that behavioral effects with both doses were significant only 1h and 1 day after withdrawal, and similar to controls at the third day. An up-regulation of D2 receptors was observed in the striatum (28% increase) but not in the hippocampus after 24h HAL (1mg/kg) withdrawal. However, an up-regulation was seen in both areas (1mg/kg) 3 days after drug withdrawal (58 and 42% increases in the hippocampus and striatum, respectively), and continued after 7 days of withdrawal only in the striatum (43 and 49% for the doses of 0.2 and 1mg/kg, respectively), suggesting the influence of dose, age, and time of drug withdrawal on these parameters. The up-regulation disappeared after 15 days of haloperidol withdrawal. Increases (72 and 140%) in constant dissociation values (K(d)) values were also observed 7 days after withdrawal. Results show differences on a time-basis between behavioral alterations and dopaminergic D2 receptors up-regulation. 相似文献
132.
Falqueto A Sessa PA Ferreira AL Vieira VP Santos CB Varejão JB Cupolillo E Porrozzi R Carvalho-Paes LE Grimaldi Júnior G 《Memórias do Instituto Oswaldo Cruz》2003,98(8):1003-1010
Between 1985 and 2000, epidemiological surveys of the American tegumentary leishmaniasis (ATL) were carried out in several rural and urban communities in Espírito Santo, Brazil. A total of 100 stocks of Leishmania (comprising isolates from both human and canine hosts with ATL) were identified by two methods of molecular characterization, using specific monoclonal antibodies and multilocus enzyme electrophoresis. Parasite isolates from 19 municipalities were found to belong to the same zymodeme and serodeme type as of the Leishmania (Viannia) braziliensis reference strain. In contrast, our genotyping studies have shown intra-specific variation among these parasites (comparisons of the variability of the internal transcribed spacers between the small and large subunits of the rRNA genes of the 22 stocks studied revealed at least 11 genotypes). Two main clusters of L. (V.) braziliensis genotypes were observed, representing parasites collected from different endemic regions in the state, where transmission reflects distinct eco-epidemiological features. Infection with this pathogen was associated with the characteristic disease forms, but neither the clinical outcome nor the response to treatment could be related to the genetic polymorphism of the isolates, as defined by using the proposed methodology. 相似文献
133.
Kobayashi A.K. Bespalhok J.C. Pereira L.F.P. Vieira L.G.E. 《Plant Cell, Tissue and Organ Culture》2003,74(1):99-102
An efficient system for in vitro plant regeneration from thin transversal stem sections explants (1–2 mm) using mature tissues of sweet orange cv. Pera was developed. Explants were cultured in different media to evaluate the frequency of regeneration and size of buds. A high percentage of explants (54% with 3.1 buds/explant) producing large buds (1–4 mm) was observed when the explants were cultivated for 2 weeks on Murashige and Skoog medium and then transferred to Woody Plant medium (WPM). Both media were supplemented with 1.8 M 6-benzylaminopurine and 0.7 M gibberellic acid. Adventitious buds were regenerated into whole plants by in vitro shoot-tip grafting. Regenerated plants started to flower after 12 months in the greenhouse, confirming their mature nature. 相似文献
134.
Mitochondria as targets of apoptosis regulation by nitric oxide 总被引:1,自引:0,他引:1
In addition to their vital role as the cell's power stations, mitochondria exert an important function in apoptosis. In response to most if not all apoptosis inducers, mitochondrial membranes are permeabilized, leading to the release of potentially toxic proteins, mostly from the intermembrane space to the rest of the cells. Such pro-apoptotic intermembrane proteins include the caspase-independent death effector AIF, as well as cytochrome c, which can trigger the activation of caspases, once it has reached the cytosol. The mitochondrial permeabilization process can be induced by a variety of different xenobiotics, via a direct effect on mitochondrial membranes. Alternatively, mitochondrial permeabilization can be induced by endogenous second messengers, which are elicited in response to stress. The permeabilization process is controlled by the mitochondrial permeability transition pore complex (PTPC), by proteins of the Bcl-2/Bax family, as well as by lipids and metabolites. Nitric oxide (NO) is one of the second messengers that can trigger apoptosis by inducing mitochondrial membrane permeabilization. This effect may involve a direct effect on the PTPC and/or indirect effects secondary to the NO-mediated inhibition of oxidative phosphorylation. This has far-reaching implications for the pathophysiology of NO. 相似文献
135.
Phagosomes fuse with late endosomes and/or lysosomes by extension of membrane protrusions along microtubules: role of Rab7 and RILP
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Harrison RE Bucci C Vieira OV Schroer TA Grinstein S 《Molecular and cellular biology》2003,23(18):6494-6506
Nascent phagosomes must undergo a series of fusion and fission reactions to acquire the microbicidal properties required for the innate immune response. Here we demonstrate that this maturation process involves the GTPase Rab7. Rab7 recruitment to phagosomes was found to precede and to be essential for their fusion with late endosomes and/or lysosomes. Active Rab7 on the phagosomal membrane associates with the effector protein RILP (Rab7-interacting lysosomal protein), which in turn bridges phagosomes with dynein-dynactin, a microtubule-associated motor complex. The motors not only displace phagosomes in the centripetal direction but, strikingly, promote the extension of phagosomal tubules toward late endocytic compartments. Fusion of tubules with these organelles was documented by fluorescence and electron microscopy. Tubule extension and fusion with late endosomes and/or lysosomes were prevented by expression of a truncated form of RILP lacking the dynein-dynactin-recruiting domain. We conclude that full maturation of phagosomes requires the retrograde emission of tubular extensions, which are generated by activation of Rab7, recruitment of RILP, and consequent association of phagosomes with microtubule-associated motors. 相似文献
136.
A relatively novel biocide, ortho-phthalaldehyde (OPA), was tested to control biofilms formed by Pseudomonas fluorescens on stainless steel surfaces. The toxic action of OPA was assessed in terms of inactivation and removal of the biofilm by means of, respectively, the determination of the respiratory activity and the variation in the dry weight of the biofilms. For comparison, the activity of OPA against suspended bacteria was also evaluated. The results showed that higher concentrations of OPA and longer exposure times are needed to inactivate P. fluorescens biofilms than planktonic populations, thus denoting that sessile bacteria have a reduced susceptibility to OPA. This appears to be associated with the reaction with the proteins of the matrix, as demonstrated by the reduction of the antimicrobial action of OPA in the presence of a protein (bovine serum albumin). The application of OPA appeared to cause little effect in the removal of biofilms from the metal slides since the mass of biofilm that remained on the surfaces, after biocide treatment, was within the same range as those observed in the control tests. These results suggest that, with OPA application, biofilms can be inactivated but stay attached to the surfaces, decreasing thereby the success of the chemical treatment. 相似文献
137.
The effects of platelet-activating factor (PAF) on the infection of peritoneal mouse macrophages by Leishmania amazonensis were investigated. Prior to the infection, the parasites and/or the macrophages were treated with PAF and/or one of the following
modulators: WEB 2086 (PAF antagonist), and the modulators of protein kinase C, phorbol-12-myristate-13-acetate (PMA), and
sphingosine. The infection was inhibited when the macrophages or both the parasites and the macrophages were treated with
PAF, but stimulated by PAF-treated parasites. WEB 2086 abrogated PAF effects in both systems. The infection was stimulated
when the macrophages were treated with sphingosine plus PAF, but inhibited when the macrophages were treated with sphingosine
and the parasites with sphingosine plus PAF. The infection was inhibited by sphingosine-treated parasites, either in the presence
or in the absence of PAF. Leishmania amazonensis–macrophage infection was inhibited by PMA in all systems tested.
Received: 27 September 2000 / Accepted: 15 December 2000 相似文献
138.
Balaban N Collins LV Cullor JS Hume EB Medina-Acosta E Vieira da Motta O O'Callaghan R Rossitto PV Shirtliff ME Serafim da Silveira L Tarkowski A Torres JV 《Peptides》2000,21(9):1301-1311
Staphylococcus aureus causes many diseases including cellulitis, keratitis, osteomyelitis, septic arthritis and mastitis. The heptapeptide RIP has been shown to prevent cellulitis in mice, which was induced by S. aureus strain Smith diffuse. Here we show that RIP can also significantly reduce the overall pathology and delay the onset of disease symptoms in several other models of S. aureus infections, including: keratitis (tested in rabbits against S. aureus 8325-4), osteomyelitis (tested in rabbits against S. aureus MS), mastitis (tested in cows against S. aureus Newbould 305, AE-1, and environmental infections) and septic arthritis (tested in mice against S. aureus LS-1). These findings substantiate that RIP is not strain specific in its inhibitory activity and that RIP is an effective inhibitor of bacterial pathology at multiple body sites following diverse routes and doses of administration. These findings strongly evidence the potential value of RIP as a chemotherapeutic agent. 相似文献
139.
The N-terminal region of the Oenococcus oeni bacteriophage fOg44 lysin behaves as a bona fide signal peptide in Escherichia coli and as a cis-inhibitory element, preventing lytic activity on oenococcal cells
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The function of the N-terminal region of the Oenococcus oeni phage fOg44 lysin (Lys44) as an export signal was investigated. We observed that when induced in Escherichia coli, Lys44 was cleaved between residues 27 and 28 in a SecA-dependent manner. Lys44 processing could be blocked by a specific signal peptidase inhibitor and was severely reduced by modification of the cleavage site. The lethal effect of Lys44 expression observed in E. coli was ascribed to the presence of its N-terminal 27-residue sequence, as its deletion resulted in the production of a nontoxic, albeit active, product. We have further established that lytic activity in oenococcal cells was dependent on Lys44 processing. An active protein with the molecular mass expected for the cleaved enzyme was detected in extracts from O. oeni-infected cells. The temporal pattern of its appearance suggests that synthesis and export of Lys44 in the infected host progress along with phage maturation. Overall, these results provide, for the first time, experimental evidence for the presence of a signal peptide in a bacteriophage lysin. Database searches and alignment of protein sequences support the prediction that other known O. oeni and Lactococcus lactis phages also encode secretory lysins. The evolutionary significance of a putative phage lysis mechanism relying on secretory lytic enzymes is tentatively discussed, on the basis of host cell wall structure and autolytic capacity. 相似文献
140.
Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction 总被引:28,自引:0,他引:28
Vieira PL de Jong EC Wierenga EA Kapsenberg ML Kaliński P 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(9):4507-4512
Dendritic cells (DC) are key initiators of primary immune responses. Myeloid DC can secrete IL-12, a potent Th1-driving factor, and are often viewed as Th1-promoting APC. Here we show that neither a Th1- nor a Th2-inducing function is an intrinsic attribute of human myeloid DC, but both depend on environmental instruction. Uncommitted immature DC require exposure to IFN-gamma, at the moment of induction of their maturation or shortly thereafter, to develop the capacity to produce high levels of IL-12p70 upon subsequent contact with naive Th cells. This effect is specific for IFN-gamma and is not shared by other IL-12-inducing factors. Type 1-polarized effector DC, matured in the presence of IFN-gamma, induce Th1 responses, in contrast to type 2-polarized DC matured in the presence of PGE2 that induce Th2 responses. Type 1-polarized effector DC are resistant to further modulation, which may facilitate their potential use in immunotherapy. 相似文献