全文获取类型
收费全文 | 15213篇 |
免费 | 982篇 |
国内免费 | 88篇 |
专业分类
耳鼻咽喉 | 156篇 |
儿科学 | 285篇 |
妇产科学 | 258篇 |
基础医学 | 2048篇 |
口腔科学 | 154篇 |
临床医学 | 1350篇 |
内科学 | 3662篇 |
皮肤病学 | 270篇 |
神经病学 | 1618篇 |
特种医学 | 707篇 |
外科学 | 2670篇 |
综合类 | 32篇 |
一般理论 | 2篇 |
预防医学 | 676篇 |
眼科学 | 138篇 |
药学 | 1021篇 |
中国医学 | 19篇 |
肿瘤学 | 1217篇 |
出版年
2024年 | 12篇 |
2023年 | 108篇 |
2022年 | 171篇 |
2021年 | 471篇 |
2020年 | 224篇 |
2019年 | 455篇 |
2018年 | 538篇 |
2017年 | 357篇 |
2016年 | 361篇 |
2015年 | 444篇 |
2014年 | 691篇 |
2013年 | 802篇 |
2012年 | 1282篇 |
2011年 | 1316篇 |
2010年 | 732篇 |
2009年 | 706篇 |
2008年 | 1062篇 |
2007年 | 1006篇 |
2006年 | 1022篇 |
2005年 | 903篇 |
2004年 | 865篇 |
2003年 | 710篇 |
2002年 | 688篇 |
2001年 | 129篇 |
2000年 | 95篇 |
1999年 | 123篇 |
1998年 | 124篇 |
1997年 | 111篇 |
1996年 | 84篇 |
1995年 | 76篇 |
1994年 | 68篇 |
1993年 | 45篇 |
1992年 | 57篇 |
1991年 | 41篇 |
1990年 | 35篇 |
1989年 | 44篇 |
1988年 | 46篇 |
1987年 | 32篇 |
1986年 | 29篇 |
1985年 | 22篇 |
1984年 | 18篇 |
1983年 | 18篇 |
1982年 | 14篇 |
1975年 | 15篇 |
1974年 | 14篇 |
1972年 | 13篇 |
1971年 | 13篇 |
1970年 | 18篇 |
1969年 | 14篇 |
1968年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 27 毫秒
91.
Background
Macrophages, upon encounter with micro-organisms or stimulated by cytokines, produce various effector molecules aimed at destroying the foreign agents and protecting the organism. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are front line molecules exerting strong cytotoxic activities against micro-organisms and many cells, including macrophages themselves. Using cells of the murine macrophage cell line (RAW 264.7) stimulated in vitro with lipopolysaccharide (LPS) and/or interferon (IFN-γ), which induce strong endogenous NO production, we examined by which mechanisms a fraction of activated macrophages protect themselves from nitrosative stress and manage to escape destruction?Results
We observed that survivors (10–50% depending on the experiments) had acquired a resistant phenotype being capable to survive when further exposed in vitro to an apoptosis inducing dose of the NO donor compound DETA-NO. These cells expressed an increased steady-state levels of Mn SOD, CuZn SOD and catalase mRNA (130–200%), together with an increased activity of the corresponding enzymes. Intracellular concentration of glutathione was also increased (× 3.5 fold at 6 hours, still maintained × 5.2 fold at 48 hours). Neither mRNA for glutathione peroxydase, γ-glutamylcysteine synthase and glutathione reductase, nor thioredoxine and thioredoxine reductase, were significantly modified. Additional experiments in which RAW 264.7 cells were stimulated with LPS and/or IFN-γ in the presence of relatively specific inhibitors of both Mn and Cu/Zn SOD, aminotriazol (ATZ) catalase inhibitor and buthionine sulfoximine (BSO) glutathione inhibitor, showed that inhibiting LPS-induced up-regulation of intracellular redox buffering systems also prevented acquisition of the resistant phenotype.Conclusions
Our data suggest a direct causal relationship between survival of a fraction of macrophages and a up-regulation of key sets of auto-protective intracellular redox buffering systems, occurring simultaneously with modulation of expression of apoptotic molecules of the Bcl2-Bcl-XL/Bax-Bad family. 相似文献92.
Stéphanie Chasseigneaux Stéphane Haïk Isabelle Laffont-Proust Olivier De Marco Martine Lenne Jean-Philippe Brandel Jean-Jacques Hauw Jean-Louis Laplanche Katell Peoc’h 《Neuroscience letters》2006
A valine to isoleucine mutation at residue 180 was identified in a French patient with Creutzfeldt-Jakob disease (CJD). The mutation is located in the close vicinity of one of the two N-glycosylation sites of the cellular prion protein (PrPC). Western blot analysis revealed accumulation in the brain of the pathogenic proteinase K-resistant PrP (PrPSc) isoform with the notable absence of the diglycosylated band. The mutant protein expressed in CHO cells was correctly glycosylated, suggesting that the atypical glycosylation pattern of PrPSc was not due to the mutation at position 180. These results suggest that the diglycosylated form of the mutant PrP180I prevents its conversion into the pathogenic mutant form PrPSc180I, supporting a central role of N-linked glycan chains in the PrP conversion process. 相似文献
93.
94.
Identification of dermatophyte species by 28S ribosomal DNA sequencing with a commercial kit 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ninet B Jan I Bontems O Léchenne B Jousson O Panizzon R Lew D Monod M 《Journal of clinical microbiology》2003,41(2):826-830
We have shown that dermatophyte species can be easily identified on the basis of a DNA sequence encoding a part of the large-subunit (LSU) rRNA (28S rRNA) by using the MicroSeq D2 LSU rRNA Fungal Sequencing Kit. Two taxa causing distinct dermatophytoses were clearly distinguished among isolates of the Trichophyton mentagrophytes species complex. 相似文献
95.
The RGD1 gene from Saccharomyces cerevisiae, which encodes a GTPase-activating protein for the Rho3 and Rho4 small G proteins, exhibits synthetic lethality with the VRP1 and LAS17 genes. Their products are proline-rich proteins that interact with both actin and myosins to ensure polarized growth. By testing functional links, we found that the VRP1 and LAS17 genes are potent suppressors of the rho3Delta mutation. In particular, they restore the polarization of actin patches in rho3Delta cells. Moreover, the vrp1Delta and las17Delta mutations were found to display a similar pattern of genetic interactions with specific actin-linked genes. These mutations also increase the sensitivity to activated forms of both Rho3p and Rho4p. These data support our working model, in which the VRP1 and LAS17 genes define a cellular complex that works in concert with the RHO3-RHO4 signaling pathway in yeast polarized growth. In addition, other observations lead us to propose that Rvs167p may act as a linking protein between the two cellular elements. 相似文献
96.
Annette Hus-Citharel Olivier Levillain François Morel 《Pflügers Archiv : European journal of physiology》1995,429(4):485-493
The distribution of arginine synthase and arginase activities along the successive nephron segments ofMeriones kidney was measured in vitro with single tubule enzymatic microtechniques making use of eitherl-[ureido-14C] Citrulline (0.108 mM) orl-[guanidion-14C]arginine (0.2 mM) as the respective substrates. Arginase activity (fmol urea formed per min per mm of tubule) was very low (5–25 fmol.min–1.mm–1) in most nephron segments including the early portions of proximal convoluted tubules (early PCT). It increased progressively after 3 mm of the PCT to reach a value of 200 fmol.min–1.mm–1 in the cortical portion of the straight proximal tubule (CPST), with a further increase, along the pars recta, of up to 250 fmol.min–1.mm–1 in the outer medullary portion (OSPST). In addition, arginase activity in OSPST and the adjacent descending thin limb (DTL) was higher in juxtamedullary nephrons (JN) than in the corresponding portions of superficial nephrons (SN). Arginine synthase activity (fmol arginine formed per mm of tubule per min) was present in proximal tubules exclusively, with a gradient decreasing along the PCT (about 600 fmol.min–1.mm–1 in the 1st mm, 65 fmol.min–1.mm–1 in CPST and 30 fmol. min–1. mm–1 in OSPST). It has been checked that CPST and OSPST (where the two enzyme systems are present) are able to convert citrulline directly into urea with a yield of 65%. It is suggested that: (1) in early PCT cells, arginine synthase activity permits the conversion of the reabsorbed citrulline into arginine (which then diffuses towards blood vessels); and (2) in pars recta cells, arginase activity results in a net entry of arginine across the basolateral membranes and in a net exit of the formed urea into the tubular fluid, if the permeability to urea of luminal membranes is greater than that of basolateral membranes. Such a mechanism of urea secretion might contribute to the maintenance of urea recycling in the medulla and, thereby, participate in the process of concentrating the urine. 相似文献
97.
Enzymatic digestion of adult human articular cartilage yields a small fraction of the total available cells 总被引:1,自引:0,他引:1
Jakob M Démarteau O Schäfer D Stumm M Heberer M Martin I 《Connective tissue research》2003,44(3-4):173-180
We investigated whether different protocols for the digestion of adult human articular cartilage influence the cell yield and capacity to attach and proliferate in culture dishes. Chondrocyte yields were expressed as a percentage of the total number of cells in the tissue, determined both histologically (using the dissector method) and biochemically (measuring the DNA content of tissue digests). Human cartilage specimens (n = 79) were digested using different protocols based on combinations of collagenase II (CGN), trypsin/EDTA, hyaluronidase, and tosyllysylchloromethane (TLCM). Yields of viable chondrocytes were the highest within a specific range of CGN concentrations and digestion times, but always < 22% of the total available cells. The combination of CGN with trypsin/EDTA or TLCM accelerated the digestion process but did not significantly increase cell yields. The percentage of viable cells that attached to culture dishes ranged 75-85% (< 19% of the total) and was reduced by TLCM. Doubling times of attached cells were comparable in all experimental groups. Our results indicate that chondrocyte yields and capacity to attach and proliferate are not highly sensitive to the specific isolation protocol used. However, typically used cartilage digestion protocols yield only a small fraction of the total available cells, possibly introducing an uncontrolled selection of certain chondrocyte subpopulations. 相似文献
98.
What and where in human audition: selective deficits following focal hemispheric lesions 总被引:8,自引:0,他引:8
Clarke S Bellmann Thiran A Maeder P Adriani M Vernet O Regli L Cuisenaire O Thiran JP 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2002,147(1):8-15
A sound that we hear in a natural setting allows us to identify the sound source and localize it in space. The two aspects
can be disrupted independently as shown in a study of 15 patients with focal right-hemispheric lesions. Four patients were
normal in sound recognition but severely impaired in sound localization, whereas three other patients had difficulties in
recognizing sounds but localized them well. The lesions involved the inferior parietal and frontal cortices, and the superior
temporal gyrus in patients with selective sound localization deficit; and the temporal pole and anterior part of the fusiform,
inferior and middle temporal gyri in patients with selective recognition deficit. These results suggest separate cortical
processing pathways for auditory recognition and localization.
Electronic Publication 相似文献
99.
Roy G Dumas C Sereno D Wu Y Singh AK Tremblay MJ Ouellette M Olivier M Papadopoulou B 《Molecular and biochemical parasitology》2000,110(2):637-206
We have expressed the reporter firefly luciferase gene (LUC) in Leishmania donovani and Leishmania major either as part of episomal vectors or integrated into the parasite genome under the control of their respective ribosomal promoter regions. An excellent linear correlation between parasite number and luciferase activity was observed with all the transfectants. LUC-expressing recombinant parasites were useful to monitor Leishmania spp. infections in macrophages or in animal models. For prolonged growth in absence of drug selection, such as within animal models, quantitation of parasites is more reliable when the reporter gene LUC is stably integrated in the parasite genome. These recombinant strains should be useful tools to monitor Leishmania growth under a number of conditions. 相似文献
100.
Identification of iduronate sulfatase gene alterations in 70 unrelated Hunter patients 总被引:4,自引:0,他引:4
Roseline Froissart Irène Maire Gilles Millat Stéphane Cudry Anne-Marie Birot Véronique Bonnet Olivier Bouton Dominique Bozon 《Clinical genetics》1998,53(5):362-368
We studied 70 unrelated Hunter patients and found a gene alteration in every patient. The molecular heterogeneity was very important. Large gene rearrangements were identified in 14 patients. Forty-three different mutations were identified in the 56 other patients and 31 were not previously described. Deletions and insertions, splice site mutations were associated with a severe phenotype as nonsense mutations except Q531X. Only a few mutations were present in several patients making difficult genotype-phenotype correlations. Mutation identification allows accurate carrier detection improving prenatal diagnosis. The mother was not found to be a carrier in five cases among the 44 sporadic cases. Haplotype analysis demonstrated a higher frequency of mutations in male meiosis. 相似文献