全文获取类型
收费全文 | 249篇 |
免费 | 34篇 |
专业分类
283篇 |
出版年
2021年 | 2篇 |
2020年 | 3篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 4篇 |
2014年 | 6篇 |
2013年 | 11篇 |
2012年 | 11篇 |
2011年 | 11篇 |
2010年 | 11篇 |
2009年 | 8篇 |
2008年 | 13篇 |
2007年 | 14篇 |
2006年 | 7篇 |
2005年 | 6篇 |
2004年 | 7篇 |
2003年 | 8篇 |
2002年 | 7篇 |
2001年 | 4篇 |
2000年 | 9篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 5篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 9篇 |
1991年 | 9篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 11篇 |
1987年 | 13篇 |
1986年 | 6篇 |
1985年 | 11篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有283条查询结果,搜索用时 0 毫秒
11.
Rynda A Maddaloni M Mierzejewska D Ochoa-Repáraz J Maslanka T Crist K Riccardi C Barszczewska B Fujihashi K McGhee JR Pascual DW 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(8):5187-5200
Mucosal tolerance induction generally requires multiple or large Ag doses. Because microfold (M) cells have been implicated as being important for mucosal tolerance induction and because reovirus attachment protein sigma1 (psigma1) is capable of binding M cells, we postulated that targeting a model Ag to M cells via psigma1 could induce a state of unresponsiveness. Accordingly, a genetic fusion between OVA and the M cell ligand, reovirus psigma1, termed OVA-psigma1, was developed to enhance tolerogen uptake. When applied nasally, not parenterally, as little as a single dose of OVA-psigma1 failed to induce OVA-specific Abs even in the presence of adjuvant. Moreover, the mice remained unresponsive to peripheral OVA challenge, unlike mice given multiple nasal OVA doses that rendered them responsive to OVA. The observed unresponsiveness to OVA-psigma1 could be adoptively transferred using cervical lymph node CD4(+) T cells, which failed to undergo proliferative or delayed-type hypersensitivity responses in recipients. To discern the cytokines responsible as a mechanism for this unresponsiveness, restimulation assays revealed increased production of regulatory cytokines, IL-4, IL-10, and TGF-beta1, with greatly reduced IL-17 and IFN-gamma. The induced IL-10 was derived predominantly from FoxP3(+)CD25(+)CD4(+) T cells. No FoxP3(+)CD25(+)CD4(+) T cells were induced in OVA-psigma1-dosed IL-10-deficient (IL-10(-/-)) mice, and despite showing increased TGF-beta1 synthesis, these mice were responsive to OVA. These data demonstrate the feasibility of using psigma1 as a mucosal delivery platform specifically for low-dose tolerance induction. 相似文献
12.
Genetic mechanisms of tumor-specific loss of 11p DNA sequences in Wilms tumor. 总被引:5,自引:7,他引:5 下载免费PDF全文
D D Dao W T Schroeder L Y Chao H Kikuchi L C Strong V M Riccardi S Pathak W W Nichols W H Lewis G F Saunders 《American journal of human genetics》1987,41(2):202-217
Wilms tumor, a common childhood renal tumor, occurs in both a heritable and a nonheritable form. The heritable form may occasionally be attributed to a chromosome deletion at 11p13, and tumors from patients with normal constitutional chromosomes often show deletion or rearrangement of 11p13. It has been suggested that a germinal or somatic mutation may occur on one chromosome 11 and predispose to Wilms tumor and that a subsequent somatic genetic event on the normal homologue at 11p13 may permit tumor development. To study the frequency and mechanism of such tumor-specific genetic events, we have examined the karyotype and chromosome 11 genotype of normal and tumor tissues from 13 childhood renal tumor patients with different histologic tumor types and associated clinical conditions. Tumors of eight of the 12 Wilms tumor patients, including all viable tumors examined directly, show molecular evidence of loss of 11p DNA sequences by somatic recombination (four cases), chromosome loss (two cases), and recombination (two cases) or chromosome loss and duplication. One malignant rhabdoid tumor in a patient heterozygous for multiple 11p markers did not show any tumor-specific 11p alteration. These findings confirm the critical role of 11p sequences in Wilms tumor development and reveal that mitotic recombination may be the most frequent mechanism by which tumors develop. 相似文献
13.
Flow cytometric evaluation of proliferative activity and ploidy in myelodysplastic syndromes and acute leukemias 总被引:1,自引:0,他引:1
A Riccardi C M Montecucco M Danova G Ucci G Mazzini P A Giordano F Pasquali 《Basic and applied histochemistry》1986,30(2):181-192
Propidium iodide (PI) DNA distribution of bone marrow (BM) cells was studied by flow cytometry (FCM) in 36 patients without hematologic or malignant disease (normal BM) and in 172 patients with anemias (36 pts), myelodysplastic syndromes (MDS) (33 pts) and acute leukemia (AL) at diagnosis (60 pts), remission (24 pts) and relapse (19 pts). White blood cells from normal male subjects were used as an external diploid reference standard (median CV = 3.8). Patients with normal BM, anemias, MDS and acute leukemia at diagnosis had tritiated thymidine labeling index (LI) and most with MDS and AL had also evaluable cytogenetics performed on the same BM sample used for FCM. In normal BM, median aliquot of cells with PI-DNA content intermediate between the diploid and the tetraploid value (2n-4n cells %) was 15.7. The ratio between the fluorescence intensity of the G0/1 peak of normal BM cells and the fluorescence intensity of the G0/1 peak of the reference standard (FI ratio) ranged from 93 to 1.05 (mean +/- 2SD). The 2n-4n cell % was higher than normal in anemias (p less than .001), lower in leukemias (p less than .001) and widely scattered in MDS. A linear correlation was found between 2n-4n cell % and LI, with 2n-4n cell % value higher than LI. The FI ratio was lower than normal in anemias (p less than .05), higher in AL with normal cytogenetics (p less than .02) and broadly scattered in MDS with normal cytogenetics. From our experience, PI-DNA-FCM is a simple and adequate method to evaluate proliferative activity in hematologic diseases. Nevertheless, caution must be taken in attributing small changes in FI ratio to aneuploidy, since they are found in anemias and in MDS and AL with normal cytogenetics, possibly due to differences in PI uptake by different cell types. 相似文献
14.
Tuberosciponoceras insolitum n. gen., n. sp. is a single dimorphic species in the Upper Albian of the Austrat Basin, southern Patagonia. The short-lived
genus was characterized by distinct ventral tubercles on all ribs and a deep, trifid internal lobe. 相似文献
15.
The excitable systems play a very important role in Biology and Medicine. Phenomena such as the transmission of impulses between neurons, the cardiac arrhythmia, the aggregation of amoebas, the appearance of organized structures in the cortex of egg cells, all derive from the activity of excitable media. In the first part of this work a general definition of excitable system is given; we then analyze some cases of excitability, distinguishing between electrical and chemical excitability and comparing experimental observations with simulations carried out by appropriate mathematical models. Such models are almost always formulated by partial differential equations of "reaction-diffusion" type and they have the characteristic to describe propagations of electrical waves (neurons, pacemaker cardiac cells, pancreatic b-cells) or chemical and mechanical waves (propagation of Ca++ waves or mechanical waves in the endoplasmic reticulum). The aim is to put in evidence that the biological systems can show not only excitability of electrical type, but also excitability of chemical nature, which can be observed in the first steps of development of egg cells or, for example, in the formation of pigments in vertebrate skin or in clam shells. 相似文献
16.
Silvia Buroni Maria R Pasca Ronald S Flannagan Silvia Bazzini Anna Milano Iris Bertani Vittorio Venturi Miguel A Valvano Giovanna Riccardi 《BMC microbiology》2009,9(1):200
Background
Burkholderia cenocepacia are opportunistic Gram-negative bacteria that can cause chronic pulmonary infections in patients with cystic fibrosis. These bacteria demonstrate a high-level of intrinsic antibiotic resistance to most clinically useful antibiotics complicating treatment. We previously identified 14 genes encoding putative Resistance-Nodulation-Cell Division (RND) efflux pumps in the genome of B. cenocepacia J2315, but the contribution of these pumps to the intrinsic drug resistance of this bacterium remains unclear. 相似文献17.
Two mechanisms are thought to be involved in the natural drug resistance of mycobacteria: the mycobacterial cell wall permeability barrier and active multidrug efflux pumps. Genes encoding drug efflux transporters have been isolated from several mycobacterial species. These proteins transport tetracycline, fluoroquinolones, aminoglycosides and other compounds. Recent reports have suggested that efflux pumps may also be involved in transporting isoniazid, one of the main drugs used to treat tuberculosis. This review highlights recent advances in our understanding of efflux-mediated drug resistance in mycobacteria, including the distribution of efflux systems in these organisms, their substrate profiles and their contribution to drug resistance. The balance between the drug transport into the cell and drug efflux is not yet clearly understood, and further studies are required in mycobacteria. 相似文献
18.
Leirla Salazar Hafida Fsihi Edda de Rossi Giovanna Riccardi Carmen Rios Stewart T. Cole Howard E. Takiff 《Molecular microbiology》1996,20(2):283-293
The genus Mycobacterium is composed of species with widely differing growth rates ranging from approximately three hours in Mycobacterium smegmatis to two weeks in Mycobacterium leprae. As DNA replication is coupled to cell duplication, it may be regulated by common mechanisms. The chromosomal regions surrounding the origins of DNA replication from M. smegmatis, M. tuberculosis, and M. leprae have been sequenced, and show very few differences. The gene order, rnpA-rpmH-dnaA-dnaN-recF-orf-gyrB-gyrA, is the same as in other Gram-positive organisms. Although the general organization in M. smegmatis is very similar to that of Streptomyces spp., a closely related genus, M. tuberculosis and M. leprae differ as they lack an open reading frame, between dnaN and recF, which is similar to the gnd gene of Escherichia coli. Within the three mycobacterial species, there is extensive sequence conservation in the intergenic regions flanking dnaA, but more variation from the consensus DnaA box sequence was seen than in other bacteria. By means of subcloning experiments, the putative chromosomal origin of replication of M. smegmatis, containing the dnaA-dnaN region, was shown to promote autonomous replication in M. smegmatis, unlike the corresponding regions from M. tuberculosis or M. leprae. 相似文献
19.
Edda De Rossi Giovanna Riccardi Anna Maria Sanangelantoni Orio Ciferri 《FEMS microbiology letters》1985,30(1-2):239-244
Abstract A Spirulina platensis gene library has been constructed using cosmid vector pMMB34. The cosmid bank was controlled for its random gene distribution by colony hybridization. Genes were identified using either homologous or heterologous probes of genes involved in photosynthesis (large and small subunit of d -ribulose 1,5-bisphosphate carboxylase, 32 kDa thylakoid protein, α, β subunits of C-phycocyanin) and protein synthesis (elongation factors EF-Tu, EF-G). 相似文献
20.
D V Delfino S Spinicelli N Pozzesi S Pierangeli E Velardi S Bruscoli M P Martelli V Pettirossi L Falchi T-b Kang C Riccardi 《Cell death and differentiation》2011,18(1):183-190
In this study, we evaluated the possible cross-talk between glucocorticoid (GC)-induced leucine zipper (Gilz) and caspase-8 in dexamethasone (Dex)-treated thymocytes. We determined that expression of Dex-induced Gilz protein was reduced when caspase-8 activity was inhibited, and this effect was not partially due to altered Gilz mRNA expression. Inhibition of the proteasome abrogated this reduction in Gilz expression, suggesting that Dex-induced caspase-8 activation protects Gilz from degradation. We hypothesized that the caspase-8-dependent protection of Gilz could be due to caspase-8-driven sumoylation. As a putative small ubiquitin-like modifier (SUMO)-binding site was identified in the Gilz sequence, we assessed whether SUMO-1 interacted with Gilz. We identified a 30-kDa protein that was compatible with the size of a Gilz–SUMO-1 complex and was recognized by the anti-SUMO-1 and anti-Gilz antibodies. In addition, Gilz bound to SUMO ubiquitin-conjugating (E2)-conjugating enzyme Ube21 (Ubc9), the specific SUMO-1 E2-conjugating enzyme, in vitro and coimmunoprecipitated with Ubc9 in vivo. Furthermore, Gilz coimmunoprecipitated with SUMO-1 both in vitro and in vivo, and this interaction depended on caspase-8 activation. This requirement for caspase-8 was further evaluated in caspase-8-deficient thymocytes and lymphocytes in which Gilz expression was reduced. In summary, our results suggest that caspase-8 activation protects Gilz from proteasomal degradation and induces its binding to SUMO-1 in GC-treated thymocytes. 相似文献