全文获取类型
收费全文 | 627篇 |
免费 | 34篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 20篇 |
妇产科学 | 5篇 |
基础医学 | 163篇 |
口腔科学 | 1篇 |
临床医学 | 68篇 |
内科学 | 122篇 |
皮肤病学 | 4篇 |
神经病学 | 50篇 |
特种医学 | 20篇 |
外科学 | 66篇 |
综合类 | 6篇 |
预防医学 | 17篇 |
眼科学 | 7篇 |
药学 | 76篇 |
中国医学 | 2篇 |
肿瘤学 | 34篇 |
出版年
2022年 | 10篇 |
2021年 | 9篇 |
2020年 | 8篇 |
2018年 | 10篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 12篇 |
2014年 | 10篇 |
2013年 | 19篇 |
2012年 | 24篇 |
2011年 | 26篇 |
2010年 | 14篇 |
2009年 | 12篇 |
2008年 | 37篇 |
2007年 | 48篇 |
2006年 | 33篇 |
2005年 | 34篇 |
2004年 | 45篇 |
2003年 | 32篇 |
2002年 | 44篇 |
2001年 | 10篇 |
2000年 | 11篇 |
1999年 | 12篇 |
1998年 | 7篇 |
1997年 | 9篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1992年 | 9篇 |
1991年 | 15篇 |
1990年 | 10篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 10篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1983年 | 6篇 |
1982年 | 3篇 |
1981年 | 7篇 |
1980年 | 4篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 8篇 |
1976年 | 4篇 |
1974年 | 6篇 |
1973年 | 3篇 |
1971年 | 7篇 |
1970年 | 4篇 |
1967年 | 4篇 |
1965年 | 3篇 |
排序方式: 共有662条查询结果,搜索用时 0 毫秒
1.
2.
A murine IgG1 monoclonal antibody, termed 68-12, was produced against purified human saposin C. Immunoprecipitation and binding analysis indicated that the antibody reacted only with saposin C. Dot blotting and Western analysis demonstrated that antibody 68-12 also reacted with prosaposin and a higher molecular weight protein(s) in murine spleen and cerebral grey matter. Solid phase competitive radioimmunoassay against 125I labeled saposin C (0.25 micrograms/ml) showed no cross reactivity for saposin A, B and D up to 15 micrograms/ml. At a concentration of 50 micrograms/ml saposin A, B and D cross reacted 21, 1.5, and 49% respectively. Monoclonal antibody 68-12 appears to have potential utility in the purification, detection and quantitation of human saposin C and its precursor. 相似文献
3.
Daniel Jirák Jan Kríz Vít Herynek Benita Andersson Peter Girman Martin Burian Frantisek Saudek Milan Hájek 《Magnetic resonance in medicine》2004,52(6):1228-1233
A promising treatment method for type 1 diabetes mellitus is transplantation of pancreatic islets containing beta-cells. The aim of this study was to develop an MR technique to monitor the distribution and fate of transplanted pancreatic islets in an animal model. Twenty-five hundred purified and magnetically labeled islets were transplanted through the portal vein into the liver of experimental rats. The animals were scanned using a MR 4.7-T scanner. The labeled pancreatic islets were clearly visualized in the liver in both diabetic and healthy rats as hypointense areas on T2*-weighted MR images during the entire measurement period. Transmission electron microscopy confirmed the presence of iron-oxide nanoparticles inside the cells of the pancreatic islets. A significant decrease in blood glucose levels in diabetic rats was observed; normal glycemia was reached 1 week after transplantation. This study, therefore, represents a promising step toward possible clinical application in human medicine. 相似文献
4.
DNA typing for class II HLA antigens with allele-specific or group-specific amplification. III. Typing for 24 alleles of HLA-DP 总被引:1,自引:0,他引:1
The second exon of HLA-DPB includes five polymorphic segments with extensive sharing of sequences between alleles. In order to facilitate assignment of specificities in heterozygous individuals, we have used group-specific amplification of two nonoverlapping sets of DPB alleles (here called group A and group B) with especially designed primers. Group A and group B polymerase chain reaction products were hybridized with sequence-specific oligonucleotide probes generating easily recognizable patterns which defined 24 distinct HLA-DPB alleles. We also established a routine procedure for distinguishing HLA-DP homozygosity from failed amplification in one of the alleles. Our results showed that when only one allele was detected, failure of amplification had occurred in less than 4% of the cases. DNA typing with this method correlated well with primed-lymphocyte typing for HLA-DP in the Tenth Workshop, as determined by us in assays performed on the workshop B-cell lines. Two normal panels of unrelated subjects were tested to obtain population frequencies. We conclude that this method is simple, relatively quick, and accurate. It is the method of choice for studies to determine the role of HLA-DP alleles in T cell reactions, in various diseases, and in transplantation. 相似文献
5.
Typing for all known MICA alleles by group-specific PCR and SSOP 总被引:8,自引:0,他引:8
Major histocompatibility complex class I chain-related gene (MICA) is a recently discovered polymorphic gene in the HLA region expressed mainly by certain epithelial cells, keratinocytes, endothelial cells, fibroblasts, and monocytes. MICA is structurally quite different from the HLA class I genes and is potentially associated with some diseases and with immune response to transplants. Some DNA-based typing techniques have previously been described for MICA including sequence-based typing (SBT) and analysis of single strand conformational polymorphisms (SSCP). In the present experiments we have developed a strategy that allows identification of all 54 MICA alleles described so far, using group-specific polymerase chain reactions (PCR) and sequence-specific oligonucleotide probes (SSOP). To analyze for the polymorphisms in exons 2, 3, and 4 an initial screening with group-specific primers, based on polymorphism at position 69 of exon 2, and at position 615-616 of exon 4, was used to determine four major groups of alleles. Then group-specific PCR amplifications were performed and the amplified DNA was hybridized with the corresponding panels of SSOP. An additional amplification was performed with locus-specific primers and hybridized with a set of SSOP to identify and/or confirm the presence of some of the alleles. Unequivocal MICA typing was achieved for 97 of 103 individuals. Of 54 previously described alleles, only 14 were observed in this population. One unexpected hybridization pattern was observed, and molecular cloning and sequencing confirmed it to be a novel sequence, which was given the local designation MICA-055D. The gene frequencies among 103 unrelated North American Caucasian donors were determined and the linkage disequilibrium between MICA and HLA-B was analyzed. 相似文献
6.
Arterial intima proteins were extracted by 9 M urea from matching histologically atheroma-free areas of 27 human thoracic aortas of both sexes from younger (15-34) and older (35-82) age groups and studied after separation by high-resolution two-dimensional polyacrylamide gel electrophoresis. Seventeen specific protein groups on each gel were identified according to their relative charges and molecular weights and their distribution in the two age groups compared. Some plasma-derived proteins occurred rarely in young aortas while they were consistently found in those from older cases, i.e., protein group 4 (alpha 1-antichymotrypsin) 1/13 (8%) vs 12/14 (86%), group 7 (haptoglobin beta-chain) 1/13 (8%) vs 13/14 (93%) and groups 6 and 9 (IgG chains) 3/13 (23%) vs 9/14 (64%), respectively. Other plasma-derived proteins such as group 3 (albumin) and 5 (alpha 1-antitrypsin) were identified in all samples of both age groups but their expression in the aortic intima increased with age. Proteins which are typically found intracellularly such as those from groups 11 (actin), 12 (cytoskeleton proteins), and 13 (tropomyosin-like proteins) appeared in samples of intima of both age groups but were less apparent in older specimens. These studies suggest that the changes in aortic intima protein distribution in the absence of atherosclerosis closely correlate with histological changes such as intimal thickening often found with aging, providing new sensitive markers of vascular senescence. 相似文献
7.
DRw6 has been difficult to define serologically. In the present experiments we have developed T cell lines in order to characterize the components of a DRw6 haplotype. This was accomplished by priming T cells with allogeneic mononuclear cells mismatched for DRw6, Dw6, and MT2. Subsequently, three sublines with distinct reactivity patterns were derived by limiting dilution. The specificities detected by these sublines included: (a) a specificity found on a subset of cells positive for DRw6 which was inhibited by monoclonal antibodies against DS(DC), the human homologue of the murine IA-encoded molecules, (b) another DRw6-associated specificity blocked by an MT2-like antibody, and (c) an MT2-like specificity blocked by monoclonal antibodies reactive with a different MT2-associated determinant. These results show that more than one IE-like, as well as the DS/DC (IA-like) molecules, carry distinctive antigenic epitopes that can be recognized by allogeneic T cells. Primed T cell lines may be useful for a better definition of certain haplotypes which are at present difficult to characterize with serological reagents alone. 相似文献
8.
Byron Peter R. Sun Zhuang Katayama Hirokazu Rypacek Frantisek 《Pharmaceutical research》1994,11(2):221-225
The pulmonary absorption kinetics of a single molecular weight distribution (MWD) of fluorophore-labeled poly-,-[N(2-hydroxyethyl)-DL-aspartamide] (F-PHEA), a hydrophilic and biocompatible synthetic polypeptide, were studied in the isolated, perfused rat lung (iprl) as functions of administered polymer concentration, dose, vehicle, and presence and absence of fluorophore. The MWD was characterized before and after absorption by measurement of weight- and number-averaged molecular weights (M
wand M
n, respectively) using high-performance gel-permeation chromatography. Values for M
w and M
n were 8.6 and 5.3 kD before, and 6.7 and 4.7 kD after, absorption into the perfusate; there was no significant metabolism and the MWD of the absorbed polymer was independent of both dose and sampling time over a 3-hr period. F-PHEA failed to show any evidence of aggregation in solution or changes in dose distribution within the airways as functions of increasing polymer concentration and dose. A concentration ranging study indicated the presence of a saturable, carrier-mediated transport process for F-PHEA with a maximum absorption rate, V
max, of approximately 180 µg or 0.027 µmol/hr. Coadministration of fluorophore-free PHEA was capable of depressing the absorption of F-PHEA. The transport process for F-PHEA appeared to have a molecular weight limit of about 7 kD for this hydrophilic polymer. 相似文献
9.
Michael B. Harbut Bhumit A. Patel Bryan K. S. Yeung Case W. McNamara A. Taylor Bright Jaime Ballard Frantisek Supek Todd E. Golde Elizabeth A. Winzeler Thierry T. Diagana Doron C. Greenbaum 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(52):21486-21491
Early secretory and endoplasmic reticulum (ER)-localized proteins that are terminally misfolded or misassembled are degraded by a ubiquitin- and proteasome-mediated process known as ER-associated degradation (ERAD). Protozoan pathogens, including the causative agents of malaria, toxoplasmosis, trypanosomiasis, and leishmaniasis, contain a minimal ERAD network relative to higher eukaryotic cells, and, because of this, we observe that the malaria parasite Plasmodium falciparum is highly sensitive to the inhibition of components of this protein quality control system. Inhibitors that specifically target a putative protease component of ERAD, signal peptide peptidase (SPP), have high selectivity and potency for P. falciparum. By using a variety of methodologies, we validate that SPP inhibitors target P. falciparum SPP in parasites, disrupt the protein’s ability to facilitate degradation of unstable proteins, and inhibit its proteolytic activity. These compounds also show low nanomolar activity against liver-stage malaria parasites and are also equipotent against a panel of pathogenic protozoan parasites. Collectively, these data suggest ER quality control as a vulnerability of protozoan parasites, and that SPP inhibition may represent a suitable transmission blocking antimalarial strategy and potential pan-protozoan drug target. 相似文献
10.
Introduction:Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening hemopoietic stem cell disorder characterized by the triad of hemolytic anemia, thrombosis, and impaired bone marrow function. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state.Patient concerns:A 27-year-old Caucasian man with PNH presented to the Emergency Department of our hospital with acute onset shortness of breath, cough and blood in urine.Diagnosis:The patient was diagnosed with acute hemolytic exacerbation of PNH complicated with moderate COVID19 pneumonia.Outcomes:The patient was initiated with an anticoagulant unfractionated heparin, dexamethasone, and cefuroxime injection. His symptoms quickly resolved, and he was discharged after 5 days.Conclusion:The complement system activation is a critical component in the sequalae of COVID19 infection. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state. Notably, C5a concentration was noted to be higher in patients with COVID19 infection. The use of complement inhibitors to attenuate immune mediated damage in COVID19 nevertheless represents a very interesting theoretical approach. However, careful consideration as to which patients may benefit will be required and the outcome of clinical trials needed. 相似文献