全文获取类型
收费全文 | 1236篇 |
免费 | 103篇 |
出版年
2023年 | 4篇 |
2022年 | 6篇 |
2021年 | 24篇 |
2020年 | 5篇 |
2019年 | 10篇 |
2018年 | 27篇 |
2017年 | 34篇 |
2016年 | 46篇 |
2015年 | 62篇 |
2014年 | 49篇 |
2013年 | 81篇 |
2012年 | 86篇 |
2011年 | 82篇 |
2010年 | 62篇 |
2009年 | 50篇 |
2008年 | 79篇 |
2007年 | 87篇 |
2006年 | 67篇 |
2005年 | 72篇 |
2004年 | 58篇 |
2003年 | 53篇 |
2002年 | 60篇 |
2001年 | 11篇 |
2000年 | 12篇 |
1999年 | 11篇 |
1998年 | 11篇 |
1997年 | 7篇 |
1996年 | 13篇 |
1995年 | 6篇 |
1994年 | 16篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 13篇 |
1989年 | 6篇 |
1988年 | 10篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 10篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1978年 | 10篇 |
1976年 | 5篇 |
1975年 | 6篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 4篇 |
排序方式: 共有1339条查询结果,搜索用时 15 毫秒
1.
Cristina Cereda Emanuela Leoni Pamela Milani Orietta Pansarasa Giuliano Mazzini Stefania Guareschi Elena Alvisi Andrea Ghiroldi Luca Diamanti Stefano Bernuzzi Mauro Ceroni Emanuela Cova 《PloS one》2013,8(10)
Several lines of evidence support the hypothesis of a toxic role played by wild type SOD1 (WT-SOD1) in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). In this study we investigated both distribution and expression profile of WT-SOD1 in leukocytes from 19 SALS patients and 17 healthy individuals. Immunofluorescence experiments by confocal microscopy showed that SOD1 accumulates in the nuclear compartment in a group of SALS subjects. These results were also confirmed by western blot carried out on soluble nuclear and cytoplasmic fractions, with increased nuclear SOD1 level (p<0.05). In addition, we observed the presence of cytoplasmic SOD1 aggregates in agreement with an increased amount of the protein recovered by the insoluble fraction. A further confirmation of the overall increased level of SOD1 has been obtained from single cells analysis using flow cytometry as cells from SALS patients showed an higher SOD1 protein content (p<0.05). These findings add further evidence to the hypothesis of an altered WT-SOD1 expression profile in peripheral blood mononuclear cells (PBMCs) from patients with ALS suggesting that WT-SOD1 species with different degrees of solubility could be involved in the pathogenesis of the disease. 相似文献
2.
Cells from a mouse B lymphoma were transfected by DQ alpha and DQ beta genes derived from a DR4 haplotype. Quantitatively, the resulting expression of human class II molecules was similar to that of human B lymphoblastoid cell lines. Qualitatively, the transformant class II molecules differed from normal class II molecules in their carbohydrate moiety. As for their antigenic specificity, they were shown to carry two determinants previously identified on DQ molecules controlled by DR4 haplotypes, i. e., DQw3 and DCHON. The transformant molecules did not carry a third DR4-associated specificity, DC5 (equivalent to TA10), and must possess a structure allelic to DC5. However, no corresponding alloantigenic specificity was detected by a screening of relevant alloantisera. 相似文献
3.
An ultrastructural analysis of the gametogenetic phases in Branchiura sowerbyi, a tubificid oligochaete, has been accomplished. These phases mostly conform to the usual pattern for the family, however, some interesting peculiarities are pointed out. The regression of sexual apparatus after reproductive period and its regeneration up to a new period of sexual maturity, has been followed throughout the year. 相似文献
4.
Y Mouneimne P F Tosi Y Gazitt C Nicolau 《Biochemical and biophysical research communications》1989,159(1):34-40
The electroporation technique, with field strengths slightly below the critical value Ec for electroporation of red blood cells (RBC), enables the insertion of xeno-proteins into the RBC membrane without damaging the cells. The electro-insertion has been used to insert biotinylated human glycophorin into human RBC membrane and human glycophorin into murine RBC membrane. Binding anti-human glycophorin antibody (10F7) to the murine RBC bearing human glycophorin indicates extracellular orientation of inserted glycophorin. Insertion of about 10(5) glycophorin molecule per cell has been estimated by whole cell ELISA. 相似文献
5.
Summary A female with chronic myelocytic leukemia (CML) in blastic phase (BP) showed a masked Ph chromosome that had originated by a translocation between chromosomes 8 and 22, with no obvious involvement of chromosome 9. A duplication of the masked Ph and trisomy 13 were present as additional anomalies. The karyotype on peripheral blood unstimulated cultures was 48,XX,t(8;22)(p12;q11),+13,+der(22) t(8;22)/47,XX,t(8;22)(p12;q11),+der(22)t(8;22). While the duplication of the Ph is a frequent finding in BP of CML, we did not find any other case in the literature with duplication of a masked Ph. In situ hybridization with c-abl and bcr probes showed that a 3 bcr sequence was translocated to the der(8) chromosome, while the c-abl oncogene was transposed to the masked Ph. 相似文献
6.
Christine C. Berte Nobuyuki Tanigaki Roberto Tosi Jack Gorski Bernard Mach 《Immunogenetics》1988,27(3):167-173
HLA class 11 molecules were isolated from mouse L cells transfected with a DR
gene and an allele, 52a, of locus DR
III from an HLA-homozygous cell line, AVL, of the DR3 haplotype. The isolated molecules were found to possess a new allospecificity, named TR81. This specificity behaved allelic to the previously described DR
III locus. The TR81 specificity was also present on the DR
I gene product of the DR3 haplotype. The nucleotide sequence of the gene encoding TR81 differs from TR81-negative DR
genes of the DRw52 family in only two codons, both located in the regions known to be involved in a gene conversion event. Consequently, the following conclusions can be formulated. (a) TR81 is a bi-locus specificity and allelic to TR22 only in its DR
III locus localization. (b) The TR81 specificity is the phenotypic counterpart of the gene conversion event which led to the generation of the DR
I gene of the DR3 haplotype. (c) One or both individual amino acid substitutions in the first domain of the DR
chain are responsible for the TR81 allospecificity. (d) Since TR81 is expressed on the DR
I chain of the DR3 haplotype, it is possible that TR81 and DR3 represent the same serological specificity. 相似文献
7.
Rosa Sorrentino Carlo Iannicola Sandro Costanzi Alberto Chersi Roberto Tosi 《Immunogenetics》1991,33(2):118-123
DNA molecules derived from three alleles of the HLA-DRB3 locus and differing from each other at several nucleotide sites were denatured and cross-hybridized. Each allelic combination was found to generate a pair of heteroduplexes of different mobility. Their retardation as compared to homoduplexes was proportional to the number of mismatches. In each heteroduplexes pair the component possessing the highest number of Pyr-Pyr oppositions was the most retarded. The results are those predicted by a theoretical model implying a correlation between base-pair opening and bending of the DNA double helix. These observations introduce a new HLA typing method at the genomic level and indicate an experimental approach to the analysis of the superhelical DNA conformation as related to different types of base oppositions. 相似文献
8.
Iron(III)-adriamycin and Iron(III)-daunorubicin complexes: physicochemical characteristics, interaction with DNA, and antitumor activity 总被引:1,自引:0,他引:1
Fe(III) complexes of two anthracyclines, adriamycin and daunorubicin, have been studied. Using potentiometric and spectroscopic measurements, we have shown that adriamycin and daunorubicin form two well-defined species with Fe(III), which can be formulated as respectively Fe(HAd)3 and Fe(HDr)3. In these formulas, HAd and HDr stand for adriamycin and daunorubicin in which the 1,4-dihydroxy-anthraquinone moiety is half-deprotonated. Both complexes are six-membered chelates. The stability constant is beta = (2.5 +/- 0.5) X 10(28) for both complexes. Interaction with DNA has been studied showing that, despite strong coordination to Fe(III), anthracyclines are able to intercalate between DNA bases pairs, releasing the metal. These complexes display antitumor activity against P 388 leukemia that compares with that of the free drug. Fe(HAd)3, unlike adriamycin, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase. Moreover, it is shown that the triferric adriamycin compound so called "quelamycin" is in fact a mixture of Fe(HAd)3 and polymeric ferric hydroxide. 相似文献
9.
Leukocyte LFA-1, OKM1, p150,95 deficiency syndrome: functional and biosynthetic studies of three kindreds 总被引:8,自引:0,他引:8
D C Anderson F C Schmalstieg W Shearer K Becker-Freeman S Kohl C W Smith M F Tosi T Springer 《Federation proceedings》1985,44(10):2671-2677
Three patients (2 female, 1 male) with recurrent infection, granulocytosis, impaired pus formation, and/or delayed umbilical cord separation were identified. Assessments of polymorphonuclear leukocytes (PMN)/monocyte function in each patient revealed profound abnormalities of adherence and adherence-dependent functions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of their PMN lysates demonstrated a deficient or absent protein(s) of 138 kilodaltons (gp 138). Na3HB4 labeling demonstrated the absence of a major cell surface glycoprotein complex in each patient. Among parental and sibling PMN suspensions, functional assessments revealed no consistent abnormalities, although variably diminished gp138 was identified by SDS-PAGE and Na3HB4 labeling. Analysis by fluorescence-activated cell sorting and monoclonal antibodies (MAb) to LFA-1 alpha, OKM1 alpha, and their common beta subunit demonstrated a severe or total deficiency of PMN/monocyte surface expression of each protein among all patients; intermediate values were observed for parental and affected sibling suspensions, findings consistent with an autosomal recessive mode of inheritance for this disorder. Cell surface labeling (125I) and immunoprecipitation with the same MAb demonstrated the absence of these glycoproteins in addition to a 150-kilodalton protein (p150,95). Identical abnormalities of surface expression of patient lymphocytes blast-transformed with phytohemagglutinin (PHA) or Epstein-Barr virus were demonstrated. Further, significantly diminished natural killer cell cytotoxicity was observed for each patient tested. PHA blast-transformed patient lymphocytes labeled with [35S]methionine demonstrated a total absence of the beta molecule but indicated the presence of an LFA-1 alpha precursor. These findings indicate that LFA-1 alpha synthesis and surface expression require beta association. It is concluded that impaired inflammatory function in this disorder is casually related to a heritable deficiency of critical "adhesive" leukocyte glycoproteins. 相似文献
10.
Analysis of the coliphage T5 DNA ejection process with free and liposome-associated TonA protein. 总被引:2,自引:0,他引:2 下载免费PDF全文
Outer membrane protein TonA, the receptor for coliphage T5, has been partially purified and incorporated into the phospholipid bilayer of liposomes. Adsorption of the phage to its receptor in either a free or liposome-associated form is fast and sufficient to trigger the ejection of encapsidated DNA. In both in vitro systems the exit of DNA from the phage capsid is a very slow process. Ejected DNA can partially accumulate inside the liposome aqueous compartment, but the transfer from the phage head to the liposome internal space is never complete, perhaps because the liposome volume is too small. The presence of polyamines or divalent cations (magnesium) or both in the incubation medium diminished the extent of DNA ejection, possibly by stabilizing DNA inside the head. DNA movement was slowed as the temperature was decreased from 37 to 18 degrees C. Furthermore, incubation at 4 degrees C totally prevented this DNA movement, even if a large part of the DNA had already exited the capsid. 相似文献