全文获取类型
收费全文 | 683篇 |
免费 | 15篇 |
专业分类
698篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 6篇 |
2019年 | 4篇 |
2018年 | 11篇 |
2017年 | 5篇 |
2016年 | 21篇 |
2015年 | 19篇 |
2014年 | 29篇 |
2013年 | 43篇 |
2012年 | 40篇 |
2011年 | 61篇 |
2010年 | 39篇 |
2009年 | 24篇 |
2008年 | 30篇 |
2007年 | 54篇 |
2006年 | 41篇 |
2005年 | 35篇 |
2004年 | 35篇 |
2003年 | 30篇 |
2002年 | 34篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 13篇 |
1997年 | 9篇 |
1996年 | 2篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1992年 | 4篇 |
1991年 | 11篇 |
1989年 | 9篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1970年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有698条查询结果,搜索用时 15 毫秒
631.
Plewka A Plewka D Madej P Nowaczyk G Sieron-Stoltny K Jakubiec-Bartnik B 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2011,49(3):398-404
We studied uterine myomas originating from females of reproductive age and from females of perimenopausal age. Uterine myomas represent benign tumors of the myometrium, and they develop frequently in women of reproductive age. The frequency of uterine myomas increases with age until women reach the menopause. The study included patients with a myomatous uterus, in the reproductive age or peri-menopausal age, independently evaluating small and large myomas. Myometrial alterations in their direct vicinity were evaluated independently of the myomas. The study included evaluation of immunolocalization of two index proteins which participate in myoma cells growth control: Ki-67 nuclear antigen and caspase 3. In women of reproductive age, both in small and large myomas, elevated immunostaining of Ki-67 was noted in parallel to low levels of caspase 3 staining, which indicated the ongoing process of proliferation. In women of peri-menopausal age with small or large myomas, no Ki-67 immunostaining was detected, while staining of caspase 3 manifested low levels. Proliferation in reproductive age women myomas is higher than in the peri-menopausal age. 相似文献
632.
Jason P. Holland Eloisi Caldas-Lopes Vadim Divilov Valerie A. Longo Tony Taldone Danuta Zatorska Gabriela Chiosis Jason S. Lewis 《PloS one》2010,5(1)
Background
The positron-emitting radionuclide 89Zr (t 1/2 = 3.17 days) was used to prepare 89Zr-radiolabeled trastuzumab for use as a radiotracer for characterizing HER2/neu-positive breast tumors. In addition, pharmacodynamic studies on HER2/neu expression levels in response to therapeutic doses of PU-H71 (a specific inhibitor of heat-shock protein 90 [Hsp90]) were conducted.Methodology/Principal Findings
Trastuzumab was functionalized with desferrioxamine B (DFO) and radiolabeled with [89Zr]Zr-oxalate at room temperature using modified literature methods. ImmunoPET and biodistribution experiments in female, athymic nu/nu mice bearing sub-cutaneous BT-474 (HER2/neu positive) and/or MDA-MB-468 (HER2/neu negative) tumor xenografts were conducted. The change in 89Zr-DFO-trastuzumab tissue uptake in response to high- and low-specific-activity formulations and co-administration of PU-H71 was evaluated by biodistribution studies, Western blot analysis and immunoPET. 89Zr-DFO-trastuzumab radiolabeling proceeded in high radiochemical yield and specific-activity 104.3±2.1 MBq/mg (2.82±0.05 mCi/mg of mAb). In vitro assays demonstrated >99% radiochemical purity with an immunoreactive fraction of 0.87±0.07. In vivo biodistribution experiments revealed high specific BT-474 uptake after 24, 48 and 72 h (64.68±13.06%ID/g; 71.71±10.35%ID/g and 85.18±11.10%ID/g, respectively) with retention of activity for over 120 h. Pre-treatment with PU-H71 was followed by biodistribution studies and immunoPET of 89Zr-DFO-trastuzumab. Expression levels of HER2/neu were modulated during the first 24 and 48 h post-administration (29.75±4.43%ID/g and 41.42±3.64%ID/g, respectively). By 72 h radiotracer uptake (73.64±12.17%ID/g) and Western blot analysis demonstrated that HER2/neu expression recovered to baseline levels.Conclusions/Significance
The results indicate that 89Zr-DFO-trastuzumab provides quantitative and highly-specific delineation of HER2/neu positive tumors, and has potential to be used to measure the efficacy of long-term treatment with Hsp90 inhibitors, like PU-H71, which display extended pharmacodynamic profiles. 相似文献633.
634.
A total of 130 various clinical materials taken from 48 children with suspected systemic fungal infection were used for the study. Clinical samples were tested by use of classical mycological procedures well as by use of molecular technique (PCR assay). The fragments of 125-bp (EO3) and 317 bp (HSP) specific for C. albicans were used for amplification. Fifty seven samples (48%) were positive for Candida albicans and eighty four (68%) by use of PCR. It should be stressed that 4 blood samples, 21 urine samples and 5 other samples were positive by use of molecular technique, only. PCR is sensitive and rapid method for detection and identification of Candida albicans from clinical materials of children with fungal infection. This technique can be applied for monitoring presence of fungal DNA in tested samples during antifungal therapy. 相似文献
635.
Moisan J Thuraisingam T Henault J De Sanctis J Radzioch D 《FEMS immunology and medical microbiology》2006,47(1):138-147
Modulation of immune responses using Toll-like receptor (TLR) ligands is fast becoming one of the main new approaches for the treatment of infectious and allergic diseases. Characterizing the role of genetic factors in modulating responses to these ligands will be crucial in determining the efficacy of a particular treatment. Our previous findings have shown that treatment of Mycobacterium bovis BCG infection with a synthetic TLR7 ligand resulted in a reduction of the splenic bacterial load only in mice carrying a wild-type allele of Nramp1. To understand further how natural resistance-associated macrophage protein 1 (NRAMP1) modulates responses to TLR7 ligands, we have analysed various important TLR7 signal transduction events in macrophage cell lines derived from B10.ANramp1r and B10.ANramp1-/- mice. The Nramp1 genotype did not affect TLR7 receptor expression, ligand uptake or intracellular processing. Following TLR7 ligand stimulation, p38 mitogen-activated protein kinase (MAPK) activation was significantly reduced in B10A.Nramp1-/- macrophages compared with B10A.Nramp1r cells. Interestingly, levels of protein kinase C zeta (PKCzeta) activation were also found to be lower in B10A.Nramp1-/- macrophages and inhibition of this kinase in B10A.Nramp1r cells led to a reduction in cytokine production. Taken together, the data demonstrate a role for NRAMP1 in modulating p38 MAPK and PKCzeta activity, which leads to reduced cytokine induction by TLR7 ligands. 相似文献
636.
Effects of growth regulators and incubation period on in vitro regeneration of adventitious shoots from gerbera petioles 总被引:4,自引:0,他引:4
Orlikowska Teresa Nowak Elzbieta Marasek Agnieszka Kucharska Danuta 《Plant Cell, Tissue and Organ Culture》1999,59(2):95-102
An effective system for in vitro regeneration of adventitious shoots from callus for the transformation or mutation of gerbera was developed. Callus was produced
from petioles of the youngest 3–4 leaves detached from auxillary shoots produced in vitro. Induction medium, on which leaves were incubated over 3 or 6 days, contained 2.3 μM thidiazuron and 0.53 μM α-naphthaleneacetic
acid. Explants were than transferred to one of three regeneration media with lower levels of growth regulators. Regeneration
was quantified over four (4-weeks each) passages at the time of explant transfer to fresh medium. Direct shoot regeneration
occurred during the first 4 weeks, and after these shoots were discarded a semi-compact organogenic callus was produced. Effectiveness
of shoot regeneration depended on four criteria: the cultivar (three cultivars were tested), the sequence of passage on regeneration
medium, the growth regulators in regeneration medium and the duration of the induction period. Regeneration potential from
calli of all cultivars increased from the first to the fourth passage. Duration of the incubation period on induction medium
(3 or 6 days) influenced regeneration to varying degrees, depending on the cultivar used and the regeneration medium contents.
There were no differences between two of the regeneration media – B, containing 2.2 μM 6-benzyladenine and 0.3 μM indole-3-acetic
acid and C, containing 4.4 μM 6-benzyladenine, 4.6 μM zeatin and 0.6 μM indole-3-acetic acid. Cultivar Mariola was the most
productive and regenerated more than seven shoots per callus in the fourth passage. Regeneration on medium B was further evaluated
on four additional gerbera cultivars.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
637.
Maria Duk Iga Steuden Danuta Dus Czeslaw Radzikowski Elwira Lisowska 《Glycoconjugate journal》1992,9(3):148-153
Human erythrocyte glycophorin was desialylated by mild acid hydrolysis and degalactosylated by Smith degradation. Two monoclonal antibodies (Tn5 and Tn56) obtained by immunization of mice with this artificial Tn antigen were characterized and compared in some experiments with two antibodies (BRIC111 and LM225) obtained in other laboratories by immunization with Tn erythrocytes. The specific binding of the antibodies to glycophorins desialylated and degalactosylated on the nitrocellulose blot and to asialo-agalactoglycophorin-coated ELISA plates, and reactions with authentic Tn antigen served for identification of their anti-Tn specificity. The antibodies were further characterized in inhibition assay with various glycoproteins. The antibody Tn5 (similar to BRIC111) was shown to be specific for human erythrocyte Tn antigen, whereas Tn56 reacted strongly with different glycoproteins carrying O-linked GalNAc- residues, and was strongly bound to the murine adenocarcinoma cell line Ta3-Ha. The antibodies Tn5, Tn56 and BRIC111 were similarly inhibited by ovine submaxillary mucin (OSM) and asialoOSM, but the antibody LM225 showed a distinct preference in reaction with OSM (sialosyl-Tn antigen). The results show that Tn antigen, obtained by chemical modifications of human glycophorin, enables the preparation and characterization of anti-Tn monoclonal antibodies, without using rare Tn erythrocytes.Abbreviations HuGph
human erythrocyte glycophorin
- HoGph
horse erythrocyte glycophorin
- OSM
ovine submaxillary mucin
- mAb
monoclonal antibody
- ELISA
enzyme-linked immunosorbent assay
- SDS-PAGE
sodium dodecylsulfate polyacrylamide gel electrophoresis
- PBS
phosphate buffered saline (0.01m Na2HPO4/0.15m NaCl, pH 7.2)
- BSA
bovine serum albumin
- TBS
0.05m Tris-HCl/0.15m NaCl, pH 7.2
- TGr
transformation grade 相似文献
638.
Danuta Rożynkowa Janina Stępień Jan Kowalewski Andrzej Nowakowski 《Human genetics》1977,39(3):293-301
Summary The R-banding pattern of the chromosomes of 31 patients hospitalized in the Hematologic Clinic for myeloid leukemia were studied before chemotherapy. This analysis permitted identification of one unusual 3-chromosome rearrangement t(3;9;22) in addition to 25 classic forms of (22q-;9q+) translocation accompanied by the specific Ph' chromosome in chronic granulocytic leukemia patients, independent of the blastic course of the disease.During blastic crisis observed in 6 patients, extra 8 and 10 chromosomes, monosomy for chromosome 17, isochromosomes 17q, translocation (12q;13q), and additional Ph' were noted.The nonrandomness of these findings is determined from results published by other authors. Their significance for the cellular phenotype is presently unknown.Supported by Grant No.422/VI of the Polish Academy of Sciences. 相似文献
639.
Summary In a cysB deletion strain a new mutation, denoted cys-2332 was isolated, which causes the constitutive expression of the cysJIH operon. cys-2332 is closely linked to cysJIH and presumably is located in the initiator region of this operon, rendering its expression independent of the cysB gene product and the internal inducer O-acetyl-L-serine. The presence of salfite reductase (encoded by cysI and cysJ) activity in a cysB
-
cys-2332 double mutant indicates that cysG, which is not linked to cysJIH but is required for the synthesis of the sulfite reductase co-factor siroheme, is not controlled by cysB. 相似文献
640.
Summary A 1,2,4-triazole resistant mutant of S. typhimurium has been isolated, in which serine transacetylase activity is seven times higher than in wild type. Partially purified serine transacetylase from a strain carrying the trz-312 mutation has kinetic properties which are virtually identical to those of the wild type enzyme and binds to O-acetylserine sulfhydrylase A to form a cysteine synthetase complex which is also indistinguishable from that found in wild type. Thus the increased activity of serine transacetylase associated with trz-312 appears to result from increased quantities of a kinetically normal, enzyme protein. Resistance to 1,2,4-triazole is probably due to the ability of trz-312 strains to synthesize O-acetyl-l-serine at a rapid enough rate to compensate for that utilized by the O-acetylserine triazolylase reaction.Genetic mapping experiments, using P1-mediated transduction, show that trz-312 is 91–99% linked to cysE, the structural gene for serine transacetylase. The results of three point crosses indicate that this mutation is located at one extreme end of the cysE locus, as would be expected for a promotor mutation. 相似文献