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排序方式: 共有398条查询结果,搜索用时 796 毫秒
1.
Michels Guido Horn Rudolf Helfen Andreas Hagendorff Andreas Jung Christian Hoffmann Beatrice Jaspers Natalie Kinkel Horst Greim Clemens-Alexander Knebel Fabian Bauersachs Johann Busch Hans-Jörg Kiefl Daniel Spiel Alexander O. Marx Gernot Dietrich Christoph F. 《Der Anaesthesist》2022,71(4):307-310
Die Anaesthesiologie - 相似文献
2.
K Decaestecker E Decaestecker C Castellani M Jaspers H Cuppens K De Boeck 《The European respiratory journal》2004,23(5):679-684
In this European study, the phenotype in 68 patients, homozygous or compound heterozygous for the G85E mutation, was investigated. Each index case was compared with two cystic fibrosis (CF) patients from the same clinic, matched for age and sex: one with pancreatic sufficiency (PS) and one with pancreatic insufficiency (PI). When comparing 31 G85E/F508del and F508del/F508del patients, there were no differences in median age at diagnosis, mean sweat chloride value, most recent weight for height, most recent forced expiratory volume in one second % predicted, prevalence of chronic Pseudomonas aeruginosa colonisation and typical CF complications. However, PI was less frequent in the G85E/F508del group. Comparison of 55 G85E patients (with second mutation known and not classified as mild) with PS controls (n=44) showed that the G85E patients had a significantly higher sweat chloride, more often failure to thrive at diagnosis, higher prevalence of PI, worse current weight for height, higher prevalence of chronic P. aeruginosa colonisation and liver cirrhosis. Pulse-chase experiments revealed that G85E cystic fibrosis transmembrane conductance regulator failed to mature on a M470 as well as on a V470 background. Therefore, G85E is a class II mutation. Although there is variability in its clinical presentation, G85E mutation results in a severe phenotype. 相似文献
3.
Cellular and molecular characteristics of an immortalized ataxia-telangiectasia (group AB) cell line 总被引:1,自引:0,他引:1
Y Ziv N G Jaspers S Etkin T Danieli L Trakhtenbrot A Amiel Y Ravia Y Shiloh 《Cancer research》1989,49(9):2495-2501
Ataxia-telangiectasia (A-T) is a multisystem hereditary disease featuring neurodegeneration, immunodeficiency, extreme cancer proneness, chromosomal instability, and radiosensitivity. A-T is found in many ethnic groups, and is genetically heterogeneous: four complementation groups have been identified in A-T so far. Attempts to isolate the A-T gene are based in part on gene transfer experiments, using permanent A-T fibroblast lines, obtained by transformation with SV40. "Immortalization" of A-T primary diploid fibroblasts using SV40 is difficult, possibly because of the chromosomal instability of these cells. The number of currently available permanent A-T fibroblast lines is small, and not all of them have been assigned to specific complementation groups. Using the assay of X-ray induced inhibition of DNA synthesis, we have assigned the A-T strain AT22IJE to complementation group AB. Origin-defective SV40 was used to transfect these cells, and one transformant (AT22IJE-T), which survived crisis, was found to have the typical characteristics of permanent cell lines obtained in this way. "In-gel renaturation" analysis did not show any DNA amplification of high degree in AT22IJE-T. Cytogenetic analysis showed considerable chromosomal instability in the new cell line, and medium conditioned by these cells contained the clastogenic activity which is characteristic of the parental strain as well. Other parameters of the "cellular A-T phenotype" have also been retained in the immortalized cells: hypersensitivity to the lethal effects of X-rays and neocarzinostatin, as well as "radioresistant" DNA synthesis. However, the sensitivity of AT22IJE-T to both DNA-damaging agents is less pronounced than that of the parental cells. The capacity of the cells for uptake of foreign DNA was tested by introducing into them the plasmid pRSVneo, using three different transfection methods. Satisfactory frequency of G418-resistant transfectants (0.66%) was achieved using a protocol recently published by Chen and Okayama (Mol. Cell Biol., 7: 2745-2752, 1987), which was found to be superior to the traditional calcium phosphate transfection method and to the polybrene-based method. 相似文献
4.
DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair 总被引:15,自引:0,他引:15 下载免费PDF全文
Wouter L. de Laat Esther Appeldoorn Kaoru Sugasawa Eric Weterings Nicolaas G.J. Jaspers Jan H.J. Hoeijmakers 《Genes & development》1998,12(16):2598-2609
The human single-stranded DNA-binding replication A protein (RPA) is involved in various DNA-processing events. By comparing the affinity of hRPA for artificial DNA hairpin structures with 3′- or 5′-protruding single-stranded arms, we found that hRPA binds ssDNA with a defined polarity; a strong ssDNA interaction domain of hRPA is positioned at the 5′ side of its binding region, a weak ssDNA-binding domain resides at the 3′ side. Polarity appears crucial for positioning of the excision repair nucleases XPG and ERCC1–XPF on the DNA. With the 3′-oriented side of hRPA facing a duplex ssDNA junction, hRPA interacts with and stimulates ERCC1–XPF, whereas the 5′-oriented side of hRPA at a DNA junction allows stable binding of XPG to hRPA. Our data pinpoint hRPA to the undamaged strand during nucleotide excision repair. Polarity of hRPA on ssDNA is likely to contribute to the directionality of other hRPA-dependent processes as well. 相似文献
5.
Predominance of null mutations in ataxia-telangiectasia 总被引:15,自引:4,他引:15
Gilad S; Khosravi R; Shkedy D; Uziel T; Ziv Y; Savitsky K; Rotman G; Smith S; Chessa L; Jorgensen TJ; Harnik R; Frydman M; Sanal O; Portnoi S; Goldwicz Z; Jaspers NG; Gatti RA; Lenoir G; Lavin MF; Tatsumi K; Wegner RD; Shiloh Y; Bar-Shira A 《Human molecular genetics》1996,5(4):433-439
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving
cerebellar degeneration, immunodeficiency, chromosomal instability,
radiosensitivity and cancer predisposition. The responsible gene, ATM, was
recently identified by positional cloning and found to encode a putative
350 kDa protein with a Pl 3-kinase-like domain, presumably involved in
mediating cell cycle arrest in response to radiation-induced DNA damage.
The nature and location of A-T mutations should provide insight into the
function of the ATM protein and the molecular basis of this pleiotropic
disease. Of 44 A-T mutations identified by us to date, 39 (89%) are
expected to inactivate the ATM protein by truncating it, by abolishing
correct initiation or termination of translation, or by deleting large
segments. Additional mutations are four smaller in-frame deletions and
insertions, and one substitution of a highly conserved amino acid at the Pl
3-kinase domain. The emerging profile of mutations causing A-T is thus
dominated by those expected to completely inactivate the ATM protein. ATM
mutations with milder effects may result in phenotypes related, but not
identical, to A-T.
相似文献
6.
Vankeerberghen A; Wei L; Jaspers M; Cassiman JJ; Nilius B; Cuppens H 《Human molecular genetics》1998,7(11):1761-1769
In order to gain a better insight into the structure and function of the
regulatory domain (RD) of the cystic fibrosis transmembrane conductance
regulator (CFTR) protein, 19 RD missense mutations that had been identified
in patients were functionally characterized. Nine of these (I601F, L610S,
A613T, D614G, I618T, L619S, H620P, G628R and L633P) resulted in aberrant
processing. No or a very small number of functional CFTR proteins will
therefore appear at the cell membrane in cells expressing these mutants.
These mutations were clustered in the N- terminal part of the RD,
suggesting that this subdomain has a folding pattern that is very sensitive
to amino acid changes. Mutations that caused no aberrant processing were
further characterized at the electrophysiological level. First, they were
studied at the whole cell level in Xenopus laevis oocytes. Mutants that
induced a whole cell current that was significantly different from
wild-type CFTR were subsequently analysed at the single channel level in
COS1 cells transiently expressing the different mutant and wild-type
proteins. Three mutant chloride channels, G622D, R792G and E822K CFTR, were
characterized by significantly lower intrinsic chloride channel activities
compared with wild-type CFTR. Two mutations, H620Q and A800G, resulted in
increased intrinsic chloride transport activities. Finally, T665S and E826K
CFTR had single channel properties not significantly different from
wild-type CFTR.
相似文献
7.
Dr. Med. C. Jaspers R. Haase H. Pfingsten G. Benker D. Reinwein 《Journal of molecular medicine (Berlin, Germany)》1993,71(7):547-551
Summary We studied the efficacy and tolerability of a repeatable long-acting parenteral depot-bromocriptine preparation (Parlodel LAR) in 14 acromegalic patients, 10 of whom had received oral bromocriptine therapy previously, 2 of them showing intolerance to oral bromocriptine. Patients received i.m. injections of 50–100 mg depot-bromocriptine at 4-week intervals for 3–24 months (median 6). Growth hormone profiles were assessed by four daily samples at 4-week intervals. Main daily growth hormone levels decreased from 52.1 ±12.3 g/l (mean ± SEM) to 19.4 ± 4.7 g/l on the day of injection. In 6 patients, growth hormone values were lowered by more than 50%, whereas IGF-I levels decreased only slightly and growth hormone values during the oral glucose tolerance test remained non-suppressible. Tumour sizes were not affected. Two women became pregnant and were delivered of healthy babies. Side-effects typical of bromocriptine occurred frequently on the days of injection and diminished in most patients after 2 months of therapy despite increasing dosage. Compared with previous oral bromocriptine therapy, 9 of 10 patients preferred the depot preparation, whereas the reduction of growth hormone levels was similar during both treatments. In conclusion, depot-bromocriptine should be considered for acromegalic patients intolerant to oral bromocriptine.Abbreviations br
Bromocriptine
- oral br.
oral bromocriptine
- depot-br.
depot-bromocriptine
- GH
growth hormone
- oGTT
oral glucose tolerance test
- GnRH
gonadotropin-releasing hormone
- TRH
thyrotropin-releasing hormone 相似文献
8.
Johnny L. Carson Laura Zhou Luisa Brighton Katherine H. Mills Haibo Zhou Ilona Jaspers 《Inhalation toxicology》2017,29(3):137-144
Objective: Mucociliary clearance sustains a baseline functionality and an “on demand” capability to upregulate clearance upon irritant exposure involving mucus hypersecretion and accelerated ciliary beat frequency (CBF) modulated by nitric oxide (NO). This study characterized these elements as well as cellular and exogenous NO concentrations subsequent to a single exposure to tobacco smoke (TS) or e-cigarette vapor (EV) on cultured human airway epithelium.Materials and methods: Air–liquid interface (ALI) airway epithelial cultures per nonsmoking human subjects were subjected to single TS or EV exposures. Measures of ciliary function and secretion were performed and cellular and exogenous NO concentrations under control and experimental conditions were assessed.Results: Both TS and EV exposures resulted similar patterns of decline in CBF within 1?min of the completion of exposure followed by a gradual return often exceeding baseline within 1?h. Post-exposure examination of exposed cultures suggested morphologic differences in secretory function relative to controls. The relative NO concentrations of TS and EV chamber air were sharply different with EV NO being only slightly elevated relative to cellular NO production.Discussion and conclusions: Epithelial remodeling and mucociliary dysfunction have been clearly associated with TS exposure. However, information contrasting epithelial structure/function following a single acute TS or EV exposure is limited. This study demonstrates a similar pattern of epithelial response to acute TS or EV exposure. Inasmuch as NO may contribute to an inflammatory milieu and generation of toxic metabolites, it is plausible that recurrent exposures over time may be contributory to chronic pathologies. 相似文献
9.
10.
Josina C. Maas Annet J. Dallmeijer Bodil Y. Oudshoorn Eline A. M. Bolster Peter A. Huijing Richard T. Jaspers 《Disability and rehabilitation》2018,40(4):398-403
Purpose state: Orthotic wearing time may be an important confounder in efficacy studies of treatment in children with spastic cerebral palsy (SCP). Most studies measure parent-reported wearing time (WTparent) with questionnaires, but it is questionable whether this yields valid results. This study aims to compare WTparent with objectively measured wearing time (WTobj) in children with SCP receiving orthotic treatment.Method: Eight children with SCP participated in this observational study. For one year, they received knee-ankle-foot orthosis (KAFO) treatment. WTparent was measured using questionnaires. WTobj was measured using temperature sensor-data-loggers that were attached to the KAFOs. The 2.5th and 97.5th percentiles and median of differences between methods (per participant) were used to calculate limits of agreement and systematic differences.Results: There was no systematic difference between WTparent and WTobj (0.1?h per week), but high inter-individual variation of the difference was found, as reflected by large limits of agreement (lower limit/2.5th percentile: ?1.7?h/week; upper limit/97.5th percentile: 11.1?h/week).Conclusions: Parent-reported wearing time (WTparent) of a KAFO differs largely from objectively measured wearing time (WTobj) using temperature sensors. Therefore, parent-reported wearing time (WTparent) of KAFOs should be interpreted with utmost care.
- Implications for Rehabilitation
Low wearing time of orthoses may be a cause of inefficacy of orthotic treatment and incorrect reported wearing time may bias results of efficacy studies.
Results of this study show that parent-reported wearing time is not in agreement with objectively measured wearing time.
Parent-reported wearing time of KAFOs should be interpreted with utmost care.
Objective methods are recommended for measuring orthotic wearing time.