全文获取类型
收费全文 | 16508篇 |
免费 | 1092篇 |
国内免费 | 92篇 |
专业分类
耳鼻咽喉 | 162篇 |
儿科学 | 355篇 |
妇产科学 | 277篇 |
基础医学 | 2249篇 |
口腔科学 | 160篇 |
临床医学 | 1502篇 |
内科学 | 4006篇 |
皮肤病学 | 284篇 |
神经病学 | 1732篇 |
特种医学 | 764篇 |
外国民族医学 | 3篇 |
外科学 | 2841篇 |
综合类 | 38篇 |
一般理论 | 2篇 |
预防医学 | 763篇 |
眼科学 | 148篇 |
药学 | 1086篇 |
中国医学 | 19篇 |
肿瘤学 | 1301篇 |
出版年
2024年 | 12篇 |
2023年 | 121篇 |
2022年 | 194篇 |
2021年 | 519篇 |
2020年 | 241篇 |
2019年 | 498篇 |
2018年 | 586篇 |
2017年 | 388篇 |
2016年 | 391篇 |
2015年 | 478篇 |
2014年 | 738篇 |
2013年 | 882篇 |
2012年 | 1357篇 |
2011年 | 1390篇 |
2010年 | 778篇 |
2009年 | 743篇 |
2008年 | 1118篇 |
2007年 | 1066篇 |
2006年 | 1093篇 |
2005年 | 948篇 |
2004年 | 920篇 |
2003年 | 757篇 |
2002年 | 722篇 |
2001年 | 165篇 |
2000年 | 136篇 |
1999年 | 154篇 |
1998年 | 138篇 |
1997年 | 124篇 |
1996年 | 94篇 |
1995年 | 81篇 |
1994年 | 77篇 |
1993年 | 53篇 |
1992年 | 89篇 |
1991年 | 62篇 |
1990年 | 54篇 |
1989年 | 66篇 |
1988年 | 62篇 |
1987年 | 58篇 |
1986年 | 47篇 |
1985年 | 37篇 |
1984年 | 26篇 |
1983年 | 22篇 |
1982年 | 17篇 |
1975年 | 16篇 |
1974年 | 16篇 |
1972年 | 19篇 |
1971年 | 14篇 |
1970年 | 21篇 |
1969年 | 15篇 |
1968年 | 10篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
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
102.
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
103.
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
104.
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
105.
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
106.
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
107.
J. Vatier C. Poitevin W. Riquet M. T. Vitre A. Olivier P. Martin S. Bonfils 《Inflammation research》1988,24(3-4):243-249
Measurements of acid and pepsin secretions and of histamine release in response to food alone or in combination with graded doses of antramine (AH), a molecular form of histamine isolated from antral mucosa, with or without somatostatin were performed simultaneously in dogs equipped with a denervated pouch.AH restored somatostatin-inhibited acid and pepsin secretions but with different intensities in regard to the different inhibitory levels induced by somatostatin.AH competitively antagonized somatostatin (1 g/kg/h) inhibition of acid cecretion, but when stronger levels of inhibition were achieved, AH restored weakly acid secretion. Recovery of pepsin secretion occured through a competitive mechanism between AH and somatostatin (1 and 2 g/kg/h). There was a close relationship between the secretory outputs and the integrated histamine responses; the slopes of the regression lines might be considered as reflecting the stimulatory activity of blood histamine on secreting cells. For acid secretion, this activity is similar in control and somatostatin (1 g/kg/h) tests, while for pepsin secretion it is identical in control and 1 or 2 g/kg/h somatostatin tests.One can speculate that the suppression of the somatostatin inhibitory effects by antramine, within the limits of physiological conditions, results from a competitive mechanism. 相似文献
108.
Berlier W Bourlet T Lawrence P Hamzeh H Lambert C Genin C Verrier B Dieu-Nosjean MC Pozzetto B Delézay O 《Journal of medical virology》2005,77(4):465-474
X4 and R5 HIV strains are present in the semen of men infected with HIV but R5 isolates are transmitted preferentially. The role of human epithelial cells in this selection is addressed. Three human cervical cell lines-CaSki, SiHa, and HEC1A-and normal human vaginal cells from HIV-negative donors were characterized for HIV receptor expression and incubated with X4 and R5 laboratory-adapted strains or primary isolates. The infection was assessed by detection of intracellular HIV DNA. The three cell lines were shown to express on their surface the CXCR4 and GalCer molecules, but not the CD4 and CCR5 ones. The three cell lines and normal human vaginal cells were found to be selectively permissive to X4 HIV entry; the preincubation of the cell lines with rhSDF-1 inhibited this infection. The detection of the intracellular proviral DNA in the cell lines and in normal human vaginal cells demonstrated a selective integration of X4 strains. Additional experiments showed that no extracellular RNA was detected in the supernatants of HEC1A cells infected by X4 isolates either after 18 days of culture or after incubation with PHA-stimulated PBMCs and that no transmission occurred after co-culture between infected HEC1A cells and PHA-stimulated PBMCs. These results suggest specific sequestration of X4 strains by genital epithelial cells, which could explain, at least in part, the HIV tropism selection process during sexual intercourse. 相似文献
109.
Escudier B Dorval T Chaput N André F Caby MP Novault S Flament C Leboulaire C Borg C Amigorena S Boccaccio C Bonnerot C Dhellin O Movassagh M Piperno S Robert C Serra V Valente N Le Pecq JB Spatz A Lantz O Tursz T Angevin E Zitvogel L 《Journal of translational medicine》2005,3(1):10-13
BACKGROUND: DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. PATIENTS AND METHODS: Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 x 1014 molecules) or peptides (10 versus 100 mug/ml) were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. RESULTS: The GMP process allowed to harvest about 5 x 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. CONCLUSION: The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration. 相似文献
110.
Immune response to lipopolysaccharide in primary biliary cirrhosis and autoimmune diseases 总被引:2,自引:0,他引:2
A bacteriological aetiology is suspected to be the triggering factor in primary biliary cirrhosis. We studied lipid A, the toxic and immunogenic moiety of gram-negative bacteria lipopolysaccharide, which accumulates abnormally in Kupffer cells, hepatocytes, and biliary epithelial cells in primary biliary cirrhosis patients. Anti-lipid A antibody levels from serum samples from 36 primary biliary cirrhosis patients, drawn before and after ursodeoxycholic acid treatment, were compared to those from patients with other liver diseases (n=236), non-hepatic diseases (n=249), and healthy subjects (n=75). In primary biliary cirrhosis patients, the prevalence of IgM anti-lipid A antibodies was higher before than after ursodeoxycholic acid therapy (64% vs 22%, respectively; P<0.001). Patients with anti-lipid A antibodies had significantly higher IgM levels than those without antibodies (8.7+/-1.1 g/l vs 4.4+/-0.8 g/l, P<0.02). Total IgM levels were correlated with anti-lipid A antibody levels (r=0.65, P<0.02). After therapy, the serum IgM levels decreased significantly (P<0.03). These results indicate that bacterial antigens may participate in the observed increase of serum IgM levels, and support an aetiological role of a gut-derived endotoxin antigen in the pathogenesis of primary biliary cirrhosis. 相似文献