全文获取类型
收费全文 | 1476篇 |
免费 | 124篇 |
出版年
2023年 | 4篇 |
2022年 | 6篇 |
2021年 | 18篇 |
2020年 | 10篇 |
2019年 | 12篇 |
2018年 | 17篇 |
2017年 | 26篇 |
2016年 | 30篇 |
2015年 | 62篇 |
2014年 | 55篇 |
2013年 | 78篇 |
2012年 | 100篇 |
2011年 | 97篇 |
2010年 | 61篇 |
2009年 | 65篇 |
2008年 | 68篇 |
2007年 | 88篇 |
2006年 | 82篇 |
2005年 | 87篇 |
2004年 | 66篇 |
2003年 | 82篇 |
2002年 | 70篇 |
2001年 | 18篇 |
2000年 | 20篇 |
1999年 | 25篇 |
1998年 | 30篇 |
1997年 | 17篇 |
1996年 | 18篇 |
1995年 | 24篇 |
1994年 | 24篇 |
1993年 | 24篇 |
1992年 | 22篇 |
1991年 | 15篇 |
1990年 | 17篇 |
1989年 | 27篇 |
1988年 | 10篇 |
1987年 | 13篇 |
1986年 | 19篇 |
1985年 | 13篇 |
1984年 | 12篇 |
1983年 | 9篇 |
1982年 | 4篇 |
1981年 | 7篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 11篇 |
1977年 | 10篇 |
1976年 | 4篇 |
1974年 | 3篇 |
1970年 | 3篇 |
排序方式: 共有1600条查询结果,搜索用时 15 毫秒
891.
Airway eosinophils accumulate in the mediastinal lymph nodes but lack antigen-presenting potential for naive T cells 总被引:8,自引:0,他引:8
van Rijt LS Vos N Hijdra D de Vries VC Hoogsteden HC Lambrecht BN 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(7):3372-3378
Asthma is characterized by infiltration of the airway wall with eosinophils. Although eosinophils are considered to be effector cells, recent studies have reported their ability to activate primed Th2 cells. In this study, we investigated whether eosinophils are capable of presenting Ag to unprimed T cells in draining lymph nodes (DLN) of the lung and compared this capacity with professional dendritic cells (DC). During development of eosinophilic airway inflammation in OVA-sensitized and challenged mice, CCR3(+) eosinophils accumulated in the DLN. To study their function, eosinophils were isolated from the bronchoalveolar lavage fluid of mice by sorting on CCR3(+)B220(-)CD3(-)CD11c(dim) low autofluorescent cells, avoiding contamination with other APCs, and were intratracheally injected into mice that previously received CFSE-labeled OVA TCR-transgenic T cells. Eosinophils did not induce divisions of T cells in the DLN, whereas DC induced on average 3.7 divisions in 45.7% of T cells. To circumvent the need for Ag processing or migration in vivo, eosinophils were pulsed with OVA peptide and were still not able to induce T cell priming in vitro, whereas DC induced vigorous proliferation. This lack of Ag-presenting ability was explained by the very weak expression of MHC class II on fresh eosinophils, despite expression of the costimulatory molecules CD80 and ICAM-1. This investigation does not support any role for airway eosinophils as APCs to naive T cells, despite their migration to the DLN at times of allergen exposure. DC are clearly superior in activating T cells in the DLN of the lung. 相似文献
892.
Kok T Hulzebos CV Wolters H Havinga R Agellon LB Stellaard F Shan B Schwarz M Kuipers F 《The Journal of biological chemistry》2003,278(43):41930-41937
The bile salt-activated farnesoid X receptor (FXR; NR1H4) controls expression of several genes considered crucial in maintenance of bile salt homeostasis. We evaluated the physiological consequences of FXR deficiency on bile formation and on the kinetics of the enterohepatic circulation of cholate, the major bile salt species in mice. The pool size, fractional turnover rate, synthesis rate, and intestinal absorption of cholate were determined by stable isotope dilution and were related to expression of relevant transporters in the livers and intestines of FXR-deficient (Fxr-/-) mice. Fxr-/- mice showed only mildly elevated plasma bile salt concentrations associated with a 2.4-fold higher biliary bile salt output, whereas hepatic mRNA levels of the bile salt export pump were decreased. Cholate pool size and total bile salt pool size were increased by 67 and 39%, respectively, in Fxr-/- mice compared with wild-type mice. The cholate synthesis rate was increased by 85% in Fxr-/- mice, coinciding with a 2.5-fold increase in cholesterol 7alpha-hydroxylase (Cyp7a1) and unchanged sterol 12alpha-hydroxylase (Cyp8b1) expression in the liver. Despite a complete absence of ileal bile acid-binding protein mRNA and protein, the fractional turnover rate and cycling time of the cholate pool were not affected. The calculated amount of cholate reabsorbed from the intestine per day was approximately 2-fold higher in Fxr-/- mice than in wild-type mice. Thus, the absence of FXR in mice is associated with defective feedback inhibition of hepatic cholate synthesis, which leads to enlargement of the circulating cholate pool with an unaltered fractional turnover rate. The absence of ileal bile acid-binding protein does not negatively interfere with the enterohepatic circulation of cholate in mice. 相似文献
893.
van Wezel GP van der Meulen J Taal E Koerten H Kraal B 《Antonie van Leeuwenhoek》2000,78(3-4):269-276
This paper describes the effects of increased expression of the cell division genes ftsZ, ftsQ, and ssgA on the development of both solid- and liquid-grown mycelium of Streptomyces coelicolor and Streptomyces lividans. Over-expression of ftsZ in S. coelicolor M145 inhibited aerial mycelium formation and blocked sporulation. Such deficient sporulation was also observed for the ftsZ mutant. Over-expression of ftsZ also inhibited morphological differentiation in S. lividans 1326, although aerial mycelium formation was less reduced. Furthermore, antibiotic production was increased in both strains, and in particular the otherwise dormant actinorhodin biosynthesis cluster of S. lividans was activated in liquid- and solid-grown cultures. No significant alterations were observed when the gene dosage of ftsQ was increased. Analysis by transmission electron microscopy of an S. coelicolor strain over-expressing ssgA showed that septum formation had strongly increased in comparison to wild-type S. coelicolor, showing that SsgA clearly influences Streptomyces cell division. The morphology of the hyphae was affected such that irregular septa were produced with a significantly wider diameter, thereby forming spore-like compartments. This suggests that ssgA can induce a process similar to submerged sporulation in Streptomyces strains that otherwise fail to do so. A working model is proposed for the regulation of septum formation and of submerged sporulation. 相似文献
894.
Krishnan L Gurnani K Dicaire CJ van Faassen H Zafer A Kirschning CJ Sad S Sprott GD 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(4):2396-2406
Vaccines capable of eliciting long-term T cell immunity are required for combating many diseases. Live vectors can be unsafe whereas subunit vaccines often lack potency. We previously reported induction of CD8(+) T cells to Ag entrapped in archaeal glycerolipid vesicles (archaeosomes). In this study, we evaluated the priming, phenotype, and functionality of the CD8(+) T cells induced after immunization of mice with OVA-Methanobrevibacter smithii archaeosomes (MS-OVA). A single injection of MS-OVA evoked a profound primary response but the numbers of H-2K(b)OVA(257-264)-specific CD8(+) T cells declined by 14-21 days, and <1% of primarily central phenotype (CD44(high)CD62L(high)) cells persisted. A booster injection of MS-OVA at 3-11 wk promoted massive clonal expansion and a peak effector response of approximately 20% splenic/blood OVA(257-264)-specific CD8(+) T cells. Furthermore, contraction was protracted and the memory pool (IL-7Ralpha(high)) of approximately 5% included effector (CD44(high)CD62L(low)) and central (CD44(high)CD62L(high)) phenotype cells. Recall response was observed even at >300 days. CFSE-labeled naive OT-1 (OVA(257-264) TCR transgenic) cells transferred into MS-OVA-immunized recipients cycled profoundly (>90%) within the first week of immunization indicating potent Ag presentation. Moreover, approximately 25% cycling of Ag-specific cells was seen for >50 days, suggesting an Ag depot. In vivo, CD8(+) T cells evoked by MS-OVA killed >80% of specific targets, even at day 180. MS-OVA induced responses similar in magnitude to Listeria monocytogenes-OVA, a potent live vector. Furthermore, protective CD8(+) T cells were induced in TLR2-deficient mice, suggesting nonengagement of TLR2 by archaeal lipids. Thus, an archaeosome adjuvant vaccine represents an alternative to live vectors for inducing CD8(+) T cell memory. 相似文献
895.
Verkade HJ Havinga R Shields DJ Wolters H Bloks VW Kuipers F Vance DE Agellon LB 《Journal of lipid research》2007,48(9):2058-2064
The phosphatidylethanolamine N-methyltransferase (PEMT) pathway of phosphatidylcholine (PC) biosynthesis is not essential for the highly specific acyl chain composition of biliary PC. We evaluated whether the PEMT pathway is quantitatively important for biliary PC secretion in mice under various experimental conditions. Biliary bile salt and PC secretion were determined in mice in which the gene encoding PEMT was inactivated (Pemt(-/-)) and in wild-type mice under basal conditions, during acute metabolic stress (intravenous infusion of the bile salt tauroursodeoxycholate), and during chronic metabolic stress (feeding a taurocholate-containing diet for 1 week). The activity of CTP:phosphocholine cytidylyltransferase, the rate-limiting enzyme of PC biosynthesis via the CDP-choline pathway, and the abundance of multi-drug-resistant protein 2 (Mdr2; encoded by the Abcb4 gene), the canalicular membrane flippase essential for biliary PC secretion, were determined. Under basal conditions, Pemt(-/-) and wild-type mice exhibited similar biliary secretion rates of bile salt and PC ( approximately 145 and approximately 28 nmol/min/100 g body weight, respectively). During acute or chronic bile salt administration, the biliary PC secretion rates increased similarly in Pemt(-/-) and control mice. Mdr2 mRNA and protein abundance did not differ between Pemt(-/-) and wild-type mice. The cytidylyltransferase activity in hepatic lysates was increased by 20% in Pemt(-/-) mice fed the basal (bile salt-free) diet (P < 0.05). We conclude that the biosynthesis of PC via the PEMT pathway is not quantitatively essential for biliary PC secretion under acute or chronic bile salt administration. 相似文献
896.
Intermolecular forces and enthalpies in the adhesion of Streptococcus mutans and an antigen I/II-deficient mutant to laminin films 下载免费PDF全文
Busscher HJ van de Belt-Gritter B Dijkstra RJ Norde W Petersen FC Scheie AA van der Mei HC 《Journal of bacteriology》2007,189(8):2988-2995
The antigen I/II family of surface proteins is expressed by most oral streptococci, including Streptococcus mutans, and mediates specific adhesion to, among other things, salivary films and extracellular matrix proteins. In this study we showed that antigen I/II-deficient S. mutans isogenic mutant IB03987 was nearly unable to adhere to laminin films under flow conditions due to a lack of specific interactions (0.8 x 10(6) and 1.1 x 10(6) cells cm(-2) at pH 5.8 and 6.8, respectively) compared with parent strain LT11 (21.8 x 10(6) and 26.1 x 10(6) cells cm(-2)). The adhesion of both the parent and mutant strains was slightly greater at pH 6.8 than at pH 5.8. In addition, atomic force microscopy (AFM) experiments demonstrated that the parent strain experienced less repulsion when it approached a laminin film than the mutant experienced. Upon retraction, combined specific and nonspecific adhesion forces were stronger for the parent strain (up to -5.0 and -4.9 nN at pH 5.8 and 6.8, respectively) than for the mutant (up to -1.5 and -2.1 nN), which was able to interact only through nonspecific interactions. Enthalpy was released upon adsorption of laminin to the surface of the parent strain but not upon adsorption of laminin to the surface of IB03987. A comparison of the adhesion forces in AFM with the adhesion forces reported for specific ligand-receptor complexes resulted in the conclusion that the number of antigen I/II binding sites for laminin on S. mutans LT11 is on the order of 6 x 10(4) sites per organism and that the sites are probably arranged along exterior surface structures, as visualized here by immunoelectron microscopy. 相似文献
897.
Molecular evolution patterns reveal life history features of mycoplasma‐related endobacteria associated with arbuscular mycorrhizal fungi 下载免费PDF全文
Mizue Naito Stephen J. Mondo Henk C. den Bakker Nicholas W. VanKuren Ylva Lekberg Joseph B. Morton Teresa E. Pawlowska 《Molecular ecology》2015,24(13):3485-3500
The mycoplasma‐related endobacteria (MRE), representing a recently discovered lineage of Mollicutes, are widely distributed across arbuscular mycorrhizal fungi (AMF, Glomeromycota). AMF colonize roots of most terrestrial plants and improve plant mineral nutrient uptake in return for plant‐assimilated carbon. The role of MRE in the biology of their fungal hosts is unknown. To start characterizing this association, we assessed partitioning of MRE genetic diversity within AMF individuals and across the AMF phylogeographic range. We further used molecular evolution patterns to make inferences about MRE codivergence with AMF, their lifestyle and antiquity of the Glomeromycota–MRE association. While we did not detect differentiation between MRE derived from different continents, high levels of diversity were apparent in MRE populations within AMF host individuals. MRE exhibited significant codiversification with AMF over ecological time and the absence of codivergence over evolutionary time. Moreover, genetic recombination was evident in MRE. These patterns indicate that, while MRE transmission is predominantly vertical, their complex intrahost populations are likely generated by horizontal transmission and recombination. Based on predictions of evolutionary theory, we interpreted these observations as a suggestion that MRE may be antagonists of AMF. Finally, we detected a marginally significant signature of codivergence of MRE with Glomeromycota and the Endogone lineage of Mucoromycotina, implying that the symbiosis between MRE and fungi may predate the divergence between these two groups of fungi. 相似文献
898.
A grapevine leafminer found recently in table grape orchards and vineyards in the Paarl region (Western Cape, South Africa) is described as Holocacista
capensis
sp. n. It has also been found on native Rhoicissus
digitata and bred on that species in the laboratory. It is closely related to Holocacista
salutans (Meyrick, 1921), comb. n. (from Antispila), described from Durban in KwaZulu-Natal, but widespread in southern Africa and a native leafminer of various Vitaceae: Rhoicissus
tomentosa, Rhoicissus
digitata, Rhoicissus
tridentata and Cissus
cornifolia. Holocacista
capensis has been found on Vitis
vinifera both in Gauteng and Western Cape, the earliest record being from 1950 in Pretoria. The initial host shift from native Vitaceae to Vitis must have occurred much earlier. The species is sometimes present in high densities, but hitherto no sizeable damage to the crops has been noted. The genus Holocacista Walsingham & Durrant, 1909, previously known from the single European grapevine leafminer Holocacista
rivillei (Stainton, 1855), is expanded and redescribed and for the first time reported from Africa, East and South-East Asia and Australia. It comprises seven named species and at least 15 unnamed species. The following species are also recombined with Holocacista: transferred from Antispilina: South-African Holocacista
varii (Mey, 2011), comb. n., feeding on Pelargonium, transferred from Antispila: the Indian species Holocacista
micrarcha (Meyrick, 1926), comb. n. and Holocacista
pariodelta (Meyrick, 1929), comb. n., both feeding on Lannea
coromandelica, and Holocacista
selastis (Meyrick, 1926), comb. n. on Psychotria
dalzelii. We also remove the following from Antispila: Heliozela
anna (Fletcher, 1920), comb. n. and Heliozela
argyrozona (Meyrick, 1918), comb. n., whereas the following Indian Vitaceae feeding species are confirmed to belong in Antispila s. str.: Antispila
argostoma Meyrick, 1916 and Antispila
aristarcha Meyrick, 1916. Holocacista
salutans and Holocacista
varii are redescribed and diagnosed against Holocacista
capensis and other South African Heliozelidae. DNA barcodes are provided for 13 species of Holocacista. 相似文献
899.
900.
Bas Brinkhof Helena TA van Tol Marian JA Groot Koerkamp Frank M Riemers Sascha G IJzer Kaveh Mashayekhi Henk P Haagsman Bernard AJ Roelen 《BMC genomics》2015,16(1)