全文获取类型
收费全文 | 402篇 |
免费 | 14篇 |
国内免费 | 29篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 26篇 |
妇产科学 | 5篇 |
基础医学 | 29篇 |
口腔科学 | 11篇 |
临床医学 | 37篇 |
内科学 | 81篇 |
皮肤病学 | 15篇 |
神经病学 | 12篇 |
特种医学 | 59篇 |
外科学 | 43篇 |
综合类 | 59篇 |
预防医学 | 12篇 |
眼科学 | 2篇 |
药学 | 33篇 |
肿瘤学 | 19篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 10篇 |
2013年 | 9篇 |
2012年 | 9篇 |
2011年 | 11篇 |
2010年 | 21篇 |
2009年 | 18篇 |
2008年 | 20篇 |
2007年 | 22篇 |
2006年 | 27篇 |
2005年 | 14篇 |
2004年 | 13篇 |
2003年 | 6篇 |
2002年 | 6篇 |
2001年 | 7篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 29篇 |
1997年 | 35篇 |
1996年 | 30篇 |
1995年 | 18篇 |
1994年 | 13篇 |
1993年 | 18篇 |
1992年 | 5篇 |
1990年 | 4篇 |
1989年 | 11篇 |
1988年 | 5篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 13篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 1篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1970年 | 1篇 |
排序方式: 共有445条查询结果,搜索用时 15 毫秒
101.
Lucila M Perrotta de Souza Jessica PL Moreira Homero S Fogaça José Marcus Raso Eulálio Ronir R Luiz Heitor SP de Souza 《Hepatobiliary & pancreatic diseases international : HBPD INT》2019,18(1):79-86
Background
Currently, surgical resection represents the only curative treatment for pancreatic cancer (PC), however, the majority of tumors are no longer resectable by the time of diagnosis. The aim of this study was to describe time trends and distribution of pancreaticoduodenectomies (PDs) performed for treating PC in Brazil in recent years.Methods
Data were retrospectively obtained from Brazilian Health Public System (namely DATASUS) regarding hospitalizations for PC and PD in Brazil from January 2008 to December 2015. PC and PD rates and their mortalities were estimated from DATASUS hospitalizations and analyzed for age, gender and demographic characteristics.Results
A total of 2364 PDs were retrieved. Albeit PC incidence more than doubled, the number of PDs increased only 37%. Most PDs were performed in men (52.2%) and patients between 50 and 69 years old (59.5%). Patients not surgically treated and those 70 years or older had the highest in-hospital mortality rates. The most developed regions (Southeast and South) as well as large metropolitan integrated municipalities registered 76.2% and 54.8% of the procedures, respectively. LMIM PD mortality fluctuated, ranging from 13.6% in 2008 to 11.8% in 2015.Conclusions
This study suggests a trend towards regionalization and volume-outcome relationships for PD due to PC, as large metropolitan integrated municipalities registered most of the PDs and more stable mortality rates. The substantial differences between PD and PC increasing rates reveals a limiting step on the health system resoluteness. Reduction in the number of hospital beds and late access to hospitalization, despite improvement in diagnostic methods, could at least in part explain these findings. 相似文献102.
Transcobalamin II (TCII) is a cobalamin (Cbl, vitamin B12)-binding protein in mammalian plasma that facilitates the cellular uptake of the vitamin. To obtain human TCII in sufficient quantity for analytical studies, the complementary DNA (cDNA) encoding TCII was inserted into the plasmid PVL 1393, and the baculovirus expressing TCII was obtained by homologous recombination in Spodoptera frugiperda (SF9) insect cells by cotransfection with the wildtype virus. Under optimized conditions, SF9 cells infected with the recombinant virus secreted 2 to 4 micrograms of TCII per milliliter of culture medium. TCII did not accumulate in the SF9 cells and seemed to be constitutively secreted as observed previously in cultured human endothelial cells. The purified recombinant TCII has the same molecular weight by SDS-PAGE as purified human TCII. The recombinant TCII cross-reacts with an antiserum to native human TCII, binds Cbl and facilitates the uptake of Cbl in eukaryotic cells by binding to the receptor for TCII-Cbl on the plasma membrane of K562 cells. Amino acid sequence analysis of the purified recombinant TCII identified two polypeptides, one identical to the amino acid sequence deduced from the cDNA and a second lacking the first and second N-terminal residues. These sequences are identical to two TCII polypeptides purified from Cohn fraction III of pooled human plasma. The two forms of recombinant TCII have the same isoelectric points as the two predominant isoprotein forms of TCII in human serum. Since the baculovirus construct contains a single cDNA that can encode only one amino acid sequence, the two isoproteins in recombinant TCII must be generated by a mechanism other than allele specific expression. A plausible mechanism for generating isoproteins of nonglycosylated peptides, such as TCII, may be by splicing of the leader peptide at alternative sites. 相似文献
103.
Hypermethylation of the 5' region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies 总被引:11,自引:0,他引:11
Baylin SB; Fearon ER; Vogelstein B; de Bustros A; Sharkis SJ; Burke PJ; Staal SP; Nelkin BD 《Blood》1987,70(2):412-417
An abnormal increase in numbers of CCGG sites methylated in the 5' region of the human calcitonin (CT) gene occurred in tumor cell DNA samples from 90% (17 of 19) of patients with non-Hodgkin's T and B cell lymphoid neoplasms and in 95% (21 of 22) of tumor cell DNA samples from patients with acute nonlymphocytic leukemia (ANLL). The changes were not seen in patients with chronic myelogenous leukemia (0 of 9). The abnormal methylation patterns appear to be a property only of transformed or malignant cells since they were not found in DNA from nonneoplastic adult tissues including sperm, early myeloid progenitor cells, benign lymphoid hyperplasia, peripheral lymphocytes stimulated to divide, or early myeloid progenitor cells (obtained by immunoaffinity using anti-My-10 antibody), but they did appear after Epstein-Barr virus transformation of lymphocytes. Moreover, during the course of therapy in patients with ANLL, the hypermethylation pattern reflects the presence of the leukemic clone even in normal-appearing granulocytes derived from this clone. The increased methylation of the CT gene may then provide an important molecular marker for biologic events in human cell transformation or tumor progression and may prove clinically useful in monitoring patients with lymphoid and acute myelogenous neoplasms. 相似文献
104.
DNA sequence analysis of the gene coding for the variant protein, factor IXLong Beach (FIXLB), has identified a transition mutation in an otherwise normal factor IX (FIX) gene. Genomic DNA clones spanning 35 kilobase (kb) pairs of the FIXLB gene were isolated. A gene analysis strategy that specifically characterized exons and their flanking intron sequences predicted the entire amino acid sequence of FIXLB. A thymine to cytosine transition causes the substitution of a threonine codon (ACA) for an isoleucine codon (ATA) in exon VIII of the FIXLB gene. This mutation results in an amino acid substitution at residue 397 of the FIX zymogen and the phenotypic display of hemophilia-B. Previous studies revealed that activated purified FIXLB (FIXaLB) had normal Ca2+, phospholipid, and factor VIIIa binding characteristics. However, FIXaLB activated factor X or factor VII (with their cofactors Ca2+ and phospholipid) at significantly reduced rates, suggesting that the defect in FIXaLB lies near or within the catalytic triad of the FIX heavy chain. Identification of an amino acid substitution near the carboxy-terminus of the FIXaLB heavy chain supports the earlier characterization of this variant protein. Moreover, our data identify a residue in the catalytic domain of FIXa essential for normal function. 相似文献
105.
The role of amino-terminal residues of the heavy chain of factor IXa in the binding of its cofactor, factor VIIIa 总被引:1,自引:0,他引:1
The purpose of this study is to determine which residues of the factor IXa heavy chain are important for interaction with the cofactor of factor IXa, factor VIIIa. Because the monoclonal antibody (MoAb) FXC008 inhibits interaction between factors IXa and VIIIa, and because it also reacts with residues 181-310 of the factor IXa heavy chain, we used the computer-modelled structure of the factor IXa heavy chain to select charged surface residues likely to interact with FXC008 and/or factor VIIIa. We made mutations in the region of residues 181-310 of the heavy chain of factor IX, and replaced these amino acids individually with those located at the same position in factor X. The mutated factor IX retained complete clotting activity and thus interacted normally with factor VIIIa. Five mutant proteins (factor IXK214F, factor IXK228R, factor IXE240Q, factor IXK247V, and factor IXN260K) reacted with heavy chain-specific MoAbs FXC008 and A-5. Neither factor IXD276K nor factor IXR248H bound to FXC008. Factor IXR252V had reduced affinity to FXC008. Our results suggest the following: (1) factor IXa residues 214, 228, 240, 247, 248, 252, 260, and 276 are not involved in specific interaction with factor VIIIa; and (2) the FXC008 and factor VIIIa binding sites may not share critical residues. 相似文献
106.
107.
108.
Sodium butyrate enhances fetal globin gene expression in erythroid progenitors of patients with Hb SS and beta thalassemia 总被引:2,自引:3,他引:2
Perrine SP; Miller BA; Faller DV; Cohen RA; Vichinsky EP; Hurst D; Lubin BH; Papayannopoulou T 《Blood》1989,74(1):454-459
Increasing the expression of the gamma globin genes is considered a useful therapeutic approach to the beta globin diseases. Because butyrate and alpha-amino-n-butyric acid (ABA) augment gamma globin expression in normal neonatal and adult erythroid progenitors, we investigated the effects of sodium butyrate and ABA on erythroid progenitors of patients with beta thalassemia and sickle cell anemia who might benefit from such an effect. Both substances increased fetal hemoglobin (Hb F) expression in Bfu-e from 7% to 30% above levels found in control cultures from the same subjects with sickle cell anemia. The fraction of cultured erythroblasts producing Hb F increased more than 20% with sodium butyrate treatment in 70% of cultures. In most cultures, this produced greater than 20% total Hb F and greater than 70% F cells, levels which have been considered beneficial in ameliorating clinical symptoms. Alpha: non-alpha (alpha-non-alpha) imbalance was decreased by 36% in erythroid progenitors of patients with beta thalassemia cultured in the presence of butyrate compared with control cultures from the same subjects. These data suggest that sodium butyrate may have therapeutic potential for increasing gamma globin expression in the beta globin diseases. 相似文献
109.
Romana SP; Poirel H; Leconiat M; Flexor MA; Mauchauffe M; Jonveaux P; Macintyre EA; Berger R; Bernard OA 《Blood》1995,86(11):4263-4269
110.
Suzuki I; Milner EC; Glas AM; Hufnagle WO; Rao SP; Pfister L; Nottenburg C 《Blood》1996,87(5):1873-1880
Many recipients of bone marrow transplant (BMT) make normal amounts of serum immunoglobulin but are deficient in generating specific antibody responses to exogenous stimuli. To determine if abnormal usage of VH genes contributes to this immunodeficiency, the usage of VH genes was determined in peripheral blood B cells of four BMT recipients, two of whom had developed chronic graft versus host disease. The pattern of usage of VH3 or VH4 genes assessed at either 90 days or approximately 1 year after transplant was similar to that observed in healthy subjects and was marked by the over utilization of two elements, one VH3 and one VH4. However, the repertoires of each of the four BMT recipients appeared to be less complex than the repertoires of healthy subjects. The differences were a consequence of the accumulation of somatic mutations among rearrangements in the controls but not in the BMT recipients. The failure to accumulate somatic mutations in rearranged VH genes is consistent with a defect in antigen driven B-cell responses. These results indicate the although the VH gene content of the repertoire has normalized by 90 days posttransplant, a maturational arrest in B-cell differentiation associated with antigen activation persists for at least 1 year after BMT. 相似文献