全文获取类型
收费全文 | 953篇 |
免费 | 83篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 61篇 |
妇产科学 | 10篇 |
基础医学 | 147篇 |
口腔科学 | 19篇 |
临床医学 | 173篇 |
内科学 | 208篇 |
皮肤病学 | 21篇 |
神经病学 | 28篇 |
特种医学 | 182篇 |
外科学 | 63篇 |
综合类 | 13篇 |
一般理论 | 1篇 |
预防医学 | 33篇 |
眼科学 | 5篇 |
药学 | 35篇 |
肿瘤学 | 36篇 |
出版年
2022年 | 4篇 |
2021年 | 16篇 |
2020年 | 8篇 |
2019年 | 17篇 |
2018年 | 22篇 |
2017年 | 10篇 |
2016年 | 14篇 |
2015年 | 13篇 |
2014年 | 20篇 |
2013年 | 30篇 |
2012年 | 24篇 |
2011年 | 28篇 |
2010年 | 35篇 |
2009年 | 29篇 |
2008年 | 37篇 |
2007年 | 27篇 |
2006年 | 43篇 |
2005年 | 32篇 |
2004年 | 24篇 |
2003年 | 17篇 |
2002年 | 12篇 |
2001年 | 21篇 |
2000年 | 22篇 |
1999年 | 20篇 |
1998年 | 41篇 |
1997年 | 51篇 |
1996年 | 48篇 |
1995年 | 40篇 |
1994年 | 22篇 |
1993年 | 23篇 |
1992年 | 13篇 |
1991年 | 19篇 |
1990年 | 11篇 |
1989年 | 24篇 |
1988年 | 34篇 |
1987年 | 30篇 |
1986年 | 27篇 |
1985年 | 15篇 |
1984年 | 7篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 15篇 |
1980年 | 10篇 |
1979年 | 9篇 |
1978年 | 12篇 |
1977年 | 11篇 |
1976年 | 8篇 |
1975年 | 10篇 |
1974年 | 9篇 |
1967年 | 2篇 |
排序方式: 共有1039条查询结果,搜索用时 15 毫秒
91.
Microbicidal properties and cytocidal selectivity of rhesus macaque theta defensins 总被引:2,自引:0,他引:2 下载免费PDF全文
Tran D Tran P Roberts K Osapay G Schaal J Ouellette A Selsted ME 《Antimicrobial agents and chemotherapy》2008,52(3):944-953
Rhesus macaque theta-defensins (RTDs) are unique macrocyclic antimicrobial peptides. The three RTDs (RTD 1-3), isolated from macaque leukocytes, have broad-spectrum antimicrobial activities in vitro and share certain structural features with acyclic porcine protegrins, which are microbicidal peptides of the cathelicidin family. To understand the structural features that confer the respective cytocidal properties to theta-defensins and protegrins, we determined and compared the biological properties of RTD 1-3 and protegrin 1 (PG-1) in assays for antimicrobial activity, bacterial membrane permeabilization, and toxicity to human cells. RTD 1-3 and PG-1 had similar microbicidal potencies against Escherichia coli, Staphylococcus aureus, and Candida albicans in low-ionic-strength (10 mM) buffers at pH 7.4. The inclusion of physiologic sodium chloride partially inhibited the microbicidal activities of the RTDs, and the degree of inhibition depended on the buffer used in the assay. Similarly, the inclusion of 10% normal human serum partially antagonized the bactericidal activities of all four peptides. In contrast, the microbicidal activities of PG-1 and RTD 1-3 against E. coli were unaffected by physiologic concentrations of calcium chloride and magnesium chloride. Treatment of E. coli ML35 cells with RTD 1-3 or PG-1 rapidly rendered the bacteria permeable to omicron-nitrophenyl-beta-D-galactopyranoside, and this was accompanied by the rapid entry of the RTDs. Finally, although PG-1 was toxic to human fibroblasts and caused a marked lysis of erythrocytes, the RTDs were not cytotoxic or hemolytic. Thus, compared to PG-1, RTD 1-3 possess substantially greater cytocidal selectivity against microbes. Surprisingly, the low cytotoxicity of the RTDs did not depend on the peptides' cyclic conformation. 相似文献
92.
Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases 总被引:1,自引:1,他引:0 下载免费PDF全文
Huijts PE Vreeswijk MP Kroeze-Jansema KH Jacobi CE Seynaeve C Krol-Warmerdam EM Wijers-Koster PM Blom JC Pooley KA Klijn JG Tollenaar RA Devilee P van Asperen CJ 《Breast cancer research : BCR》2007,9(6):R78-9
Introduction
Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.Methods
We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.Results
Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.Conclusion
Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles. 相似文献93.
Saunders LP Ouellette A Bandle R Chang WC Zhou H Misra RN De La Cruz EM Braddock DT 《Molecular cancer therapeutics》2008,7(10):3352-3362
Autotaxin (ATX) is a prometastatic enzyme initially isolated from the conditioned medium of human melanoma cells that stimulates a myriad of biological activities, including angiogenesis and the promotion of cell growth, survival, and differentiation through the production of lysophosphatidic acid (LPA). ATX increases the aggressiveness and invasiveness of transformed cells, and ATX levels directly correlate with tumor stage and grade in several human malignancies. To study the role of ATX in the pathogenesis of malignant melanoma, we developed antibodies and small-molecule inhibitors against recombinant human protein. Immunohistochemistry of paraffin-embedded human tissue shows that ATX levels are markedly increased in human primary and metastatic melanoma relative to benign nevi. Chemical screens identified several small-molecule inhibitors with binding constants ranging from nanomolar to low micromolar. Cell migration and invasion assays with melanoma cell lines show that ATX markedly stimulates melanoma cell migration and invasion, an effect suppressed by ATX inhibitors. The migratory phenotype can be rescued by the addition of the enzymatic product of ATX, LPA, confirming that the observed inhibition is linked to suppression of LPA production by ATX. Chemical analogues of the inhibitors show structure-activity relationships important for ATX inhibition and indicate pathways for their optimization. These studies suggest that ATX is an approachable molecular target for the rational design of chemotherapeutic agents directed against malignant melanoma. 相似文献
94.
Expression and purification of functional recombinant epitopes for the platelet antigens, PlA1 and PlA2 总被引:1,自引:1,他引:1
The platelet antigens, PlA1 and PlA2, are responsible for most cases of posttransfusion purpura (PTP) and neonatal alloimmune thrombocytopenia (NAIT) in the caucasian population and are determined by two allelic forms of the platelet glycoprotein GPIIIa gene. To study the interaction between these antigens and their respective antibodies, we inserted the sequence that encodes the signal peptide and the N- terminal 66 amino acids of the PlA1 form of GPIIIa into the expression vector pGEX1. To express the PlA2 antigen, nucleotide 196 of the PlA1 coding sequence was mutated to the PlA2 allelic form. When transformed and induced in Escherichia coli, the two constructs produce glutathione S-transferase (GST)/N-terminal GPIIIa fusion proteins, one containing leucine at position 33 (PlA1), the other proline (PlA2). These proteins are easily purified in milligram quantities using glutathione-Sepharose and react specifically with their respective antibodies by immunoblot and enzyme-linked immunosorbent assay. Antigenicity of the PlA1 fusion protein in reduced glutathione increases with time; moreover, the addition of oxidized glutathione accelerates this process, presumably because of formation of the native disulfide bonds. Neutralization assays indicate that the PlA1 fusion protein competes for all of the anti-PlA1 antibody in the serum of patients with PTP and NAIT that is capable of interacting with the surface of intact platelets. This study shows that the GST/N-terminal GPIIIa fusion proteins contain conformational epitopes that mimic those involved in alloimmunization, and that regions other than the amino terminal 66 amino acids of GPIIIa are not likely to contain or be required for the development of functional PlA1 epitopes. Furthermore, these recombinant proteins can be used for the affinity-purification of clinical anti-PlA1 antibodies and specific antibody identification by western blotting, making them useful in the diagnosis of patients alloimmunized to PlA1 alloantigens. 相似文献
95.
Solitary bronchioloalveolar carcinoma: CT criteria 总被引:14,自引:0,他引:14
Kuhlman JE; Fishman EK; Kuhajda FP; Meziane MM; Khouri NF; Zerhouni EA; Siegelman SS 《Radiology》1988,167(2):379-382
The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis. 相似文献
96.
97.
To understand better the relationships between blood-group antigens and bacterial constituents, examples of 23 gram-negative bacteria (representing the 10 genera Citrobacter, Edwardsiella, Enterobacter, Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Serratia, and Shigella) were tested for the presence of Kl-like antigens by hemagglutination-inhibition (HAI) assays against both IgG and IgM anti-Kl. Saline-suspended whole organisms, cell-free culture media, and disrupted organisms were used to test for such antigens in, on, and secreted by the microorganisms examined. Disrupted organisms of an isolate of Shigella sonnei nonspecifically inhibited IgG anti-Kl as well as IgG antibodies of the specificities Kpb, Fya, S, and c. However, only Escherichia coli 0125:B15, subtype 12808, had specific K1-like activity (no activity with other IgG [(k, Kpb, Jka, Fya, S, c] and IgM [A, B, M, P1] antibodies). Disrupted organisms inhibited IgM but not IgG anti-K1 in the HAI assay. A second subtype, E. coli 0125:B15, subtype 12809, exhibited no K1-like activity. These findings support the report of K1 activity in cell-free broth cultures of E. coli 0125:B15 (subtype unspecified). Thus, although not all E. coli 0125:B15 possesses K1-like activity, the finding of such activity in at least one E. coli subtype confirms the idea that bacterial components may play a role in the production of naturally occurring antibodies directed against non-ABO red cell antigens. 相似文献
98.
Anton A. Semenistyy Elena A. Litvina EA Anna G. Fedotova Chukwuweike Gwam Andrey N. Mironov 《Injury》2019,50(2):515-520
Background
Intramedullary nailing is considered a “gold standard” for treatment of tibial shaft fractures. However, some types of fractures are typically considered as “difficult for nailing”. This group includes the periarticular fractures, fractures of both bones at the same level, comminuted and segmental fractures of the tibia. Fixator-assisted nailing (FAN) is an effective method treatment of these types of fractures. The main requirements for the ideal reduction device are an ease of its installation and an ability of multiplanar fracture reduction. Fixator-assisted nailing (FAN) with the use of two perpendicular to each other monolateral tubular frames perfectly meets these requirements. In this study we present this new surgical technique and the analysis of first 30 cases.Methods
A prospective analysis was conducted for 30 patients with “difficult for nailing” tibial fractures treated with fixator-assisted nailing in our institution between September 1st, 2017, and March 1st, 2018. The duration of surgery and its different stages, the time of fluoroscopy, difficulties encountered during surgery, were analyzed. Clinical and radiological methods were used to evaluated reduction quality.Results
In all 30 cases the acceptable reduction was achieved. The mean duration of the surgical procedure was 73.7?±?3?min. The mean duration of fluoroscopy 85.9?±?4.8?s. In 7 cases we faced with technical difficulties, which were successfully addressed.Conclusion
The described technique of FAN is an effective method for the treatment of “difficult for nailing” tibial fractures. Future multi-centered studies with a larger number of patients are needed to validate our results. 相似文献99.
100.