全文获取类型
收费全文 | 14814篇 |
免费 | 937篇 |
国内免费 | 95篇 |
专业分类
耳鼻咽喉 | 124篇 |
儿科学 | 495篇 |
妇产科学 | 347篇 |
基础医学 | 2145篇 |
口腔科学 | 251篇 |
临床医学 | 1311篇 |
内科学 | 3612篇 |
皮肤病学 | 448篇 |
神经病学 | 1561篇 |
特种医学 | 307篇 |
外科学 | 1308篇 |
综合类 | 41篇 |
一般理论 | 7篇 |
预防医学 | 1257篇 |
眼科学 | 278篇 |
药学 | 1130篇 |
中国医学 | 40篇 |
肿瘤学 | 1184篇 |
出版年
2024年 | 23篇 |
2023年 | 202篇 |
2022年 | 512篇 |
2021年 | 859篇 |
2020年 | 406篇 |
2019年 | 614篇 |
2018年 | 671篇 |
2017年 | 412篇 |
2016年 | 478篇 |
2015年 | 560篇 |
2014年 | 704篇 |
2013年 | 924篇 |
2012年 | 1289篇 |
2011年 | 1279篇 |
2010年 | 764篇 |
2009年 | 590篇 |
2008年 | 914篇 |
2007年 | 895篇 |
2006年 | 791篇 |
2005年 | 718篇 |
2004年 | 585篇 |
2003年 | 514篇 |
2002年 | 474篇 |
2001年 | 63篇 |
2000年 | 38篇 |
1999年 | 68篇 |
1998年 | 85篇 |
1997年 | 77篇 |
1996年 | 42篇 |
1995年 | 31篇 |
1994年 | 32篇 |
1993年 | 22篇 |
1992年 | 22篇 |
1991年 | 15篇 |
1990年 | 16篇 |
1989年 | 6篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 13篇 |
1985年 | 8篇 |
1984年 | 6篇 |
1983年 | 13篇 |
1982年 | 8篇 |
1981年 | 6篇 |
1980年 | 9篇 |
1979年 | 5篇 |
1977年 | 9篇 |
1975年 | 4篇 |
1974年 | 10篇 |
1973年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
41.
Epitope of the vaccine-type Bordetella pertussis strain 186 lipooligosaccharide and antiendotoxin activity of antibodies directed against the terminal pentasaccharide-tetanus toxoid conjugate 下载免费PDF全文
Niedziela T Letowska I Lukasiewicz J Kaszowska M Czarnecka A Kenne L Lugowski C 《Infection and immunity》2005,73(11):7381-7389
Lipooligosaccharides (LOS) isolated from Bordetella pertussis strains 186 and 606 were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-resolution magic angle spinning nuclear magnetic resonance (NMR). These analyses distinguished between the LOS of strains 186 and 606, suggesting that the structure of LOS in B. pertussis is heterogeneous. The pentasaccharide was selectively cleaved from LOS of B. pertussis strain 186, purified, and covalently linked to a monomer fraction of tetanus toxoid. Injection of rabbits with the neoglycoconjugate emulsified in complete Freund's adjuvant yielded immunoglobulin G antibodies that were reactive with the LOS. These antibodies reacted strongly with B. pertussis LOS possessing the complete dodecasaccharide, as determined by an enzyme-linked immunosorbent assay, immunoblotting, and flow cytometry with intact, live bacterial cells. The binding epitope within the pentasaccharide was investigated by saturation transfer difference (STD) NMR spectroscopy. Protons H-1 and H-4 of the terminal alpha-D-GlcpNAc and proton H-6 and protons of an N-methyl group at H-4 of 3-substituted beta-L-FucpNAc4NMe exhibited the largest saturation transfers. STD NMR experiments confirmed that the immunodominant epitope recognized by the antineoglycoconjugate antibodies is located predominantly in the distal trisaccharide of B. pertussis 186 LOS. The antipentasaccharide antibodies induced by the conjugate inhibited the secretion of tumor necrosis factor alpha, interleukin-6, and NO by LOS-stimulated J774A.1 cells. 相似文献
42.
Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling 总被引:35,自引:2,他引:35 下载免费PDF全文
Athena W. Lin Marta Barradas James C. Stone Linda van Aelst Manuel Serrano Scott W. Lowe 《Genes & development》1998,12(19):3008-3019
Oncogenic Ras transforms immortal rodent cells to a tumorigenic state, in part, by constitutively transmitting mitogenic signals through the mitogen-activated protein kinase (MAPK) cascade. In primary cells, Ras is initially mitogenic but eventually induces premature senescence involving the p53 and p16INK4a tumor suppressors. Constitutive activation of MEK (a component of the MAPK cascade) induces both p53 and p16, and is required for Ras-induced senescence of normal human fibroblasts. Furthermore, activated MEK permanently arrests primary murine fibroblasts but forces uncontrolled mitogenesis and transformation in cells lacking either p53 or INK4a. The precisely opposite response of normal and immortalized cells to constitutive activation of the MAPK cascade implies that premature senescence acts as a fail-safe mechanism to limit the transforming potential of excessive Ras mitogenic signaling. Consequently, constitutive MAPK signaling activates p53 and p16 as tumor suppressors. 相似文献
43.
Moreno Sabater A Moreno M Moreno FJ Eguiluz C van Rooijen N Benito A 《Parasitology research》2005,95(2):97-105
The main objective of this study was to determine whether a chemical immunomodulation protocol could reduce the resistance of NOD/LtSz-SCID mice to Plasmodium falciparum infection and provide an improved mouse model for screening the antimalarial activity of new compounds. This model was compared with the presently used immunodeficient Beige/Nude/Xid (BNX) mouse model, using the same protocol, in terms of percentage of infected mice, parasite development, leukocyte response and phagocytosis of P. falciparum infected cells in various organs. Our results show that the combination of the chemical immune modulation protocol with the genetic background of NOD/LtSz-SCID mice results in the development of long-lasting P. falciparum infection in a high percentage of mice. A comparison of the results obtained in the histological study for both mouse models suggests that the higher rate of success in NOD/LtSz-SCID mice could be related to the reduced macrophage recruitment developed in different tissues to remove the parasite from blood. 相似文献
44.
45.
Andrade MM Tomé MF Santiago ES Lúcia-Santos A de Andrade TG 《Physiology & behavior》2003,78(1):125-133
We conducted a longitudinal study about daily variation of Wistar male rats' behavior in the elevated plus-maze (EPM) evaluated in the 1st, 2nd, 3rd, 6th, 12th, and 18th months of life. Animals were submitted to the plus-maze in 12 sessions at 2-h intervals (n=72, 6 per time point). Spontaneous rest-activity rhythm of four animals was assessed by observation of 24-h videotape records. Time series were analyzed by Cosinor method. Behavioral rates on the six occasions and in light and dark phases were compared by means of two-way ANOVA with repeated measures. Exploratory behavior in EPM was smaller in the light phase and in older animals. Higher values of open and closed arms exploration were observed in the first and third months of the dark phase, and in the first month of the light phase. Adjustment to the 24-h period was significant at all stages for rest-activity data, number of entries in closed arms, and time on center, and for three to five stages for open-arm exploration. In general, 24 h variability was more pronounced in younger animals compared with older ones. The present study showed that: (1). a significant amount of total variability of the behavioral indexes analyzed could be attributed to 24 h variation, (2). light/dark phases differences in EPM exploration were present at all developmental stages, (3). older Wistar rats explored less the EPM and were less active in their home cage compared with younger ones, and (4). behavioral indexes (EPM) decrease was phase related and partially related to a reorganization of rest-activity rhythm. 相似文献
46.
Neoplastic cells generally present profound changes in glucose metabolism. The mechanisms underlying such process are numerous and all may involve altered cellular hormonal responses. Here we report the first evidence that cellular location of phosphofructokinase activity in human breast cancer tissues is different from the one observed in control tissues and that this phenomenon may be involved in the increased glycolytic flux observed in those cells. Through co-sedimentation techniques, we observed that 60% of phosphofructokinase activity in neoplastic tissues is located in an actin-enriched fraction, against 36% in control tissues. Additionally, metastatic tumor tissues presented a two fold increase in this particulate activity when compared to non-metastatic tumor samples. We propose that the alteration in cellular distribution of phosphofructokinase activity in human breast cancer tissues is a mechanism associated to the process of cell transformation and may be a consequence of the altered hormonal milieu observed in several types of cancer. 相似文献
47.
A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins that bind the regulatory subunits of protein kinase A (PKA). AKAP binding to PKA regulates the phosphorylation of various proteins, some of which have been implicated in synaptic plasticity and memory consolidation. Here we show that the regulatory subunits of PKA are colocalized with AKAP150 (an AKAP isoform that is expressed in the brain) in the lateral amygdala (LA) and that infusion to the LA of the peptide St-Ht31, which blocks PKA anchoring onto AKAPs, impairs memory consolidation of auditory fear conditioning. 相似文献
48.
Prospective Cohort Study of Enterotoxigenic Escherichia coli Infections in Argentinean Children 下载免费PDF全文
Gloria I. Viboud Mabel J. Jouve Norma Binsztein Marta Vergara Marta Rivas Marina Quiroga Ann-Mari Svennerholm 《Journal of clinical microbiology》1999,37(9):2829-2833
In a follow-up study, enterotoxigenic Escherichia coli (ETEC) infections in 145 children from two communities located in northeastern Argentina were monitored for 2 years. The occurrence of diarrhea was monitored by weekly household visits. Of 730 fecal specimens collected, 137 (19%) corresponded to diarrheal episodes. ETEC was isolated from a significantly higher proportion of symptomatic (18.3%) than asymptomatic (13.3%) children (P = 0.04541). Individuals of up to 24 months of age were found to have a higher risk of developing ETEC diarrhea than older children (odds ratio [OR], 3.872; P = 0.00021). When the toxin profiles were considered, only heat stable enterotoxin (ST)-producing ETEC was directly associated with diarrhea (P = 0.00035). Fifty-five percent of the ETEC isolated from symptomatic children and 19% of the ETEC isolated from asymptomatic children expressed one of the colonization factors (CFs) investigated, i.e., CF antigen I (CFA/I), CFA/II, CFA/III, and CFA/IV; coli surface antigens CS7 and CS17; and putative CFs PCFO159, PCFO166, and PCFO20, indicating a clear association between diarrhea and ETEC strains that carry these factors (P = 0.0000034). The most frequently identified CFs were CFA/IV (16%), CFA/I (10%), and CS17 (9%). CFs were mostly associated with ETEC strains that produce ST and both heat-labile enterotoxin and ST. Logistic regression analysis, applied to remove confounding effects, revealed that the expression of CFs was associated with illness independently of the toxin type (OR, 4.81; P = 0.0003). When each CF was considered separately, CS17 was the only factor independently associated with illness (OR, 16.6; P = 0.0151). Most CFs (the exception was CFA/IV) fell within a limited array of serotypes, while the CF-negative isolates belonged to many different O:H types. These results demonstrate that some CFs are risk factors for the development of ETEC diarrhea. 相似文献
49.
Marta Pacio Miguez Fernando Santos‐Simarro Sixto García‐Miñaúr Ramón Velázquez Fragua Ángela del Pozo Mario Solís Carmen Jiménez Rodríguez Virginia Rufo‐Rabadán Victoria Eugenia Fernandez Inmaculada Rueda Maria Victoria Gomez del Pozo Natividad Gallego Pablo Lapunzina María Palomares‐Bralo 《American journal of medical genetics. Part A》2020,182(10):2222-2225
50.
Gopalraj RK Zhu H Kelly JF Mendiondo M Pulliam JF Bennett DA Estus S 《Neurobiology of aging》2005,26(1):1-7
The low density lipoprotein receptor (LDLR) is an attractive candidate gene for genetic association with Alzheimer's disease (AD) because: (i) the LDLR is an apolipoprotein E (apoE) receptor, alleles of which have been associated with AD, (ii) LDLR resides at chromosome 19p13.3 within a region linked to AD, and (iii) LDLR modulates the homeostasis of cholesterol, which itself appears associated with AD. Therefore, we evaluated whether LDLR haplotypes alter the odds of AD by performing an association study examining three LDLR single nucleotide polymorphisms (SNPs) in 118 AD patients and 133 non-AD subjects. LDLR genotypes were obtained by TaqMan allelic discrimination assays. Although individual LDLR SNPs were not associated with AD, analyses of unambiguous haplotypes suggested the hypothesis that the 211 LDLR haplotype was associated with reduced odds of AD. We then evaluated this hypothesis in a second study cohort, i.e., the Religious Orders Study. These results supported the hypothesis that the 211 LDLR haplotype is associated with reduced odds of AD. Moreover, these data suggested further associations between LDLR variants and AD. Thus, LDLR variants appear significantly associated with AD and merit additional study. 相似文献