全文获取类型
收费全文 | 13721篇 |
免费 | 745篇 |
国内免费 | 75篇 |
学科分类
医药卫生 | 14541篇 |
出版年
2023年 | 91篇 |
2022年 | 78篇 |
2021年 | 456篇 |
2020年 | 230篇 |
2019年 | 308篇 |
2018年 | 449篇 |
2017年 | 273篇 |
2016年 | 348篇 |
2015年 | 368篇 |
2014年 | 515篇 |
2013年 | 659篇 |
2012年 | 1090篇 |
2011年 | 1107篇 |
2010年 | 605篇 |
2009年 | 611篇 |
2008年 | 979篇 |
2007年 | 971篇 |
2006年 | 917篇 |
2005年 | 805篇 |
2004年 | 736篇 |
2003年 | 647篇 |
2002年 | 665篇 |
2001年 | 107篇 |
2000年 | 110篇 |
1999年 | 132篇 |
1998年 | 119篇 |
1997年 | 118篇 |
1996年 | 96篇 |
1995年 | 86篇 |
1994年 | 79篇 |
1993年 | 65篇 |
1992年 | 48篇 |
1991年 | 56篇 |
1990年 | 62篇 |
1989年 | 66篇 |
1988年 | 48篇 |
1987年 | 39篇 |
1986年 | 34篇 |
1985年 | 28篇 |
1984年 | 48篇 |
1983年 | 40篇 |
1982年 | 26篇 |
1981年 | 25篇 |
1980年 | 24篇 |
1978年 | 19篇 |
1977年 | 25篇 |
1976年 | 14篇 |
1975年 | 15篇 |
1974年 | 19篇 |
1972年 | 14篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
Rosenzweig SD Schäffer AA Ding L Sullivan R Enyedi B Yim JJ Cook JL Musser JM Holland SM 《Clinical immunology (Orlando, Fla.)》2004,112(1):113-119
Different polymorphisms have been described in the minimal promoter region (MPR) of the interferon-gamma receptor 1 (IFNGR1), a molecule that plays a critical role in mycobacterial control. We sequenced the IFNGR1 MPR from African American, Caucasian and Korean controls, and from mycobacteria-infected patients. Six different single nucleotide polymorphisms (SNPs) were detected in the IFNGR1 MPR. The three ethnic groups showed different SNP distribution patterns, but no significant differences were detected between mycobacterial cases and controls. Two polymorphisms were found in all populations (G-611A, T-56C). We cloned the four allelic variants (var) of haplotype G-611A/T-56C into a luciferase reporter vector and determined their promoter activity. Polymorphisms at position -611 had a stronger effect on the promoter activity than those at position -56, and constructs carrying G-611 produced a stronger promoter activity than -611A constructs. The IFNGR1 MPR is a polymorphic region with at least two SNPs influencing its activity, but these are not associated with increased mycobacterial susceptibility. 相似文献
82.
Torti C Quiros-Roldan E Monno L Patroni A Saracino A Angarano G Tinelli C Lo Caputo S Tirelli V Mazzotta F Carosi G;MASTER Cohort GenPheRex Study Group;MASTER Cohort PhenGen Study Group 《Journal of medical virology》2004,74(1):29-33
This study aimed at identifying HIV-1 protease amino acid changes associated with protease inhibitor (PI) exposure and susceptibility. New amino acid substitutions were correlated with the number of experienced PIs, reaching statistical significance only for those at positions 3, 44, and 74. The correspondence multivariate model demonstrated that > or =3 experienced PIs and substitutions or mutations at positions 3, 46, 54, 73, 74, and 84 were correlated with PI cross-resistance, including resistance for lopinavir and amprenavir in this cohort of patients who were naive for these drugs. 相似文献
83.
Structural investigations of cross-linked hyaluronan. 总被引:3,自引:0,他引:3
Amelia Gamini Sergio Paoletti Renato Toffanin Fulvio Micali Luigi Michielin Carla Bevilacqua 《Biomaterials》2002,23(4):1161-1167
Structural properties of several cross-linked hyaluronan derivatives, obtained by scanning electron microscopy, monodimensional NMR microscopy and small angle X-ray scattering of synchrotron radiation, are presented and compared with those observed for non-modified hyaluronic acid, used as a reference material. The experimental results, obtained in different media, showed a consistent picture of the synthesized matrices. In particular, the presence of zones of denser polymeric material observed by electron microscopy resulted in a higher transversal relaxation rate of the bulk water protons as well as in a decrease of the diffusion coefficient obtained by NMR microscopy. Moreover, the presence of polymer junction zones gave rise to the appearance of a well-defined correlation peak in the pattern of intensity of the scattered X-radiation. 相似文献
84.
Expression of human CD81 in transgenic mice does not confer susceptibility to hepatitis C virus infection 总被引:6,自引:0,他引:6
Masciopinto F Freer G Burgio VL Levy S Galli-Stampino L Bendinelli M Houghton M Abrignani S Uematsu Y 《Virology》2002,304(2):187-196
We previously demonstrated that hepatitis C virus (HCV) binds to human CD81 through the E2 glycoprotein. Therefore, expression of the human CD81 molecule in transgenic mice was expected to provide a new tool to study HCV infection in vivo, as the chimpanzee is the only species currently available as a laboratory animal model that can be infected with HCV. We produced transgenic mice expressing the human CD81 protein in a wide variety of tissues. We confirmed binding of recombinant E2 glycoprotein to the liver tissue as well as to thymocytes and splenic lymphocytes in the transgenic mice. We inoculated chimpanzee plasma infected with HCV into these animals. None of these transgenic animals showed evidence of viral replication. Furthermore, human CD81 transgenic mice that lack expression of endogenous mouse CD81 were also resistant to HCV infection. We conclude that expression of human CD81 alone is insufficient to confer susceptibility to HCV infection in the mouse. The presence of additional possible factors for HCV infection is discussed. 相似文献
85.
Ignazio Di Fazio Massimo Motta Salvatore Musumeci Sergio Neri Giovanni Pistone Mariano Malaguarnera 《Journal of interferon & cytokine research》2004,24(10):594-599
Determination of serum iron levels in patients affected by chronic hepatitis C is considered fundamental for studying the response to interferon-alpha (IFN-alpha) treatment. IFN could induce anemia, which is promptly corrected by exogenous administration of recombinant human erythropoietin (rHuEPO). The aim of our study was to verify the possible beneficial effect of rHuEPO in patients affected by chronic hepatitis C and treated with IFN. Seventy consecutive patients (42 males and 28 females, mean age 46.4+/-5.2 years) affected by chronic hepatitis C were enrolled. In all patients, chronic hepatitis C was diagnosed on the basis of clinical and biological findings (alanine aminotransferase [ALT] serum levels at least 2-fold higher than normal values for at least 12 months and the presence of anti-HCV antibodies). All patients were negative for hepatitis B virus (HBV) infection, hepatitis D virus (HDV infection, and HIV infection. Statistical analysis was carried out using the Wilcoxon nonparametric sum rank test, the Spearman correlation rank test, and the Friedman ANOVA and Kendall coefficient of concordance. At the end of the treatment, our study series showed significant differences in serum levels of AST (p < 0.001), iron (p < 0.001), and ferritin (p < 0.001). At the end of the follow-up period, significant differences were seen in ALT, aspartate (AST), and iron ferritin and transferrin levels. All differences favored patients who received IFN-alpha and rHuEPO. We think that the depletion of circulating iron may improve the immune response impaired by iron accumulation in the liver. Our study confirms the important role played by iron in the response to IFN treatment, suggesting that the use of rHuEPO induces a better response to IFN in patients with chronic hepatitis C by activation of erythropoiesis. 相似文献
86.
da Cunha JP Nakayasu ES Elias MC Pimenta DC Téllez-Iñón MT Rojas F Muñoz MJ Manuel M Almeida IC Schenkman S 《Molecular and biochemical parasitology》2005,140(1):75-86
Histone H1 of most eukaryotes is phosphorylated during the cell cycle progression and seems to play a role in the regulation of chromatin structure, affecting replication and chromosome condensation. In trypanosomatids, histone H1 lacks the globular domain and is shorter when compared with the histone of other eukaryotes. We have previously shown that in Trypanosoma cruzi, the agent of Chagas' disease, histone H1 is phosphorylated and this increases its dissociation from chromatin. Here, we demonstrate using mass spectrometry analysis that T. cruzi histone H1 is only phosphorylated at the serine 12 in the sequence SPKK, a typical cyclin-dependent kinase site. We also found a correlation between the phosphorylation state of histone H1 and the cell cycle. Hydroxyurea and lactacystin, which, respectively, arrest parasites at the G1/S and G2/M stages of the cell cycle, increased the level of histone H1 phosphorylation. Cyclin-dependent kinase-related enzymes TzCRK3, and less intensely the TzCRK1 were able to phosphorylate histone H1 in vitro. Histone H1 dephosphorylation was prevented by treating the parasites with okadaic acid but not with calyculin A. These findings suggest that T. cruzi histone H1 phosphorylation is promoted by cyclin dependent kinases, present during S through G2 phase of the cell cycle, and its dephosphorylation is promoted by specific phosphatases. 相似文献
87.
Núñez M Maida I Babudieri S Fenu L Camino N González-Lahoz J Mura MS Soriano V 《HIV clinical trials》2005,6(2):103-106
Complex reciprocal interactions between hepatitis C (HCV) and hepatitis B (HBV) viruses (HBV) have been reported. We examined the influence of HBV on HCV RNA titers in 376 HCV/HIV-coinfected patients (30 were also HBsAg positive). Regression analyses identified negative HBsAg and male sex as factors associated with HCV RNA values >500,000 IU/mL. 相似文献
88.
Lipid abnormalities in HIV-infected patients are not correlated with lopinavir plasma concentrations
89.
The melanocortin 1 receptor (MC1R) gene is a major determinant of human pigmentation and specific allelic variants have been associated with red hair and sun sensitive skin types as well as increased skin cancer risk in Caucasian individuals. We screened for allelic variants the entire MC1R coding region of 100 unrelated individuals sampled from an Italian population who has darker pigmentary traits than populations analyzed to date. Twenty MC1R variants were identified, eighteen located at non-synonymous sites and two at synonymous sites. We report four novel MC1R allelic variants: C35Y (g.104G>A), V38M (g.112G>A), L44V (g.130C>G) and I120T (g.359T>C). 相似文献
90.
Lauren E. Sergio David J. Ostry 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1995,105(1):123-137
The present study quantifies electromyographic (EMG) magnitude, timing, and duration in one and two degree of freedom elbow movements involving combinations of flexion-extension and pronation-supination. The aim is to understand the organization of commands subserving motion in individual and multiple degrees of freedom. The muscles tested in this study fell into two categories with respect to agonist burst magnitude: those whose burst magnitude varied with motion in a second degree of freedom at the elbow, and those whose burst magnitude depended on motion in one degree of freedom only. In multiarticular muscles contributing to motion in two degrees of freedom at the elbow, we found that the magnitude of the agonist burst was greatest for movements in which a muscle acted as agonist in both degrees of freedom. The burst magnitudes for one degree of freedom movements were, in turn, greater than for movements in which the muscle was agonist in one degree of freedom and antagonist in the other. It was also found that, for movements in which a muscle acted as agonist in two degrees of freedom, the burst magnitude was, in the majority of cases, not different from the sum of the burst magnitudes in the component movements. When differences occurred, the burst magnitude for the combined movement was greater than the sum of the components. Other measures of EMG activity such as burst onset time and duration were not found to vary in a systematic manner with motion in these two degrees of freedom. It was also seen that several muscles which produced motion in one degree of freedom at the elbow, including triceps brachii (long head), triceps brachii (lateral head), and pronator quadratus displayed first agonist bursts whose magnitude did not vary with motion in a second degree of freedom. However, for the monoarticular elbow flexors brachialis and brachioradialis, agonist burst magnitude was affected by pronation or supination. Lastly, it was observed that during elbow movements in which muscles acted as agonist in one degree of freedom and antagonist in the other, the muscle activity often displayed both agonist and antagonist components in the same movement. It was found that, for pronator teres and biceps brachii, the timing of the bursts was such that there was activity in these muscles concurrent with activity in both pure agonists and pure antagonists. The empirical summation of EMG burst magnitudes and the presence in a single muscle of both agonist and antagonist bursts within a movement suggest that central commands associated with motion in individual degrees of freedom at the elbow may be superimposed to produce elbow movements in two degrees of freedom. 相似文献