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31.
Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA 总被引:2,自引:2,他引:2
Rozmahel R; Gyomorey K; Plyte S; Nguyen V; Wilschanski M; Durie P; Bear CE; Tsui LC 《Human molecular genetics》1997,6(7):1153-1162
We have used a mouse model to study the ability of human CFTR to correct
the defect in mice deficient of the endogenous protein. In this model,
expression of the endogenous Cftr gene was disrupted and replaced with a
human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for
the gene replacement failed to show neither improved intestinal pathology
nor survival when compared to mice completely lacking CFTR. RNA analyses
showed that the human CFTR sequence was transcribed from the targeted
allele in the respiratory and intestinal epithelial cells. Furthermore, in
vivo potential difference measurements showed that basal CFTR chloride
channel activity was present in the apical membranes of both nasal and
rectal epithelial cells in all homozygous knock-in animals examined. Ussing
chamber studies showed, however, that the cAMP-mediated chloride channel
function was impaired in the intestinal tract among the majority of
homozygous knock-in animals. Hence, failure to correct the intestinal
pathology associated with loss of endogenous CFTR was related to
inefficient functional expression of the human protein in mice. These
results emphasize the need to understand the tissue- specific expression
and regulation of CFTR function when animal models are used in gene therapy
studies.
相似文献
32.
Successful outcome with day 4 embryo transfer after preimplantation diagnosis for genetically transmitted diseases 总被引:4,自引:5,他引:4
Preimplantation genetic diagnosis was performed in 61 day 3 embryos
obtained by in-vitro fertilization from seven patient carriers of
haemophilia, Marfan's syndrome, Bloch-Sulzemberg syndrome (incontinentia
pigmentosa) or X chromosome-linked immune deficiency, retinitis pigmentosa,
and FG syndrome, which is characterized by mental retardation and
hypotonia. After multiplex polymerase chain reaction, 16 embryos were
diagnosed as being unaffected, and these were transferred to the uterus on
the following day (day 4). Of these embryos, six (37.5%) implanted,
resulting in the delivery of a singleton and a twin pregnancy, a late
second trimester miscarriage (twins at week 20) and a first trimester
miscarriage at week 8. All the diagnoses were confirmed by amniocentesis.
We report for the first time a late day 4 transfer of biopsied human
embryos undergoing preimplantation genetic diagnosis. This transfer
schedule allows an extra day to perform genetic analyses on single
blastomeres and to monitor any adverse effect of the biopsy procedure.
相似文献
33.
Marjolijn Bornebroek Joost Haan Marion LC Maat-Schieman Sjoerd G Van Duinen Raymund AC Roos 《Brain pathology (Zurich, Switzerland)》1996,6(2):111-114
Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of β-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma.
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article 相似文献
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article 相似文献
34.
Rocha-Rodrigues DB Paschoini G Pereira SA dos Reis MA Teixeira Vde P Rodrigues Júnior V 《Clinical and diagnostic laboratory immunology》2003,10(5):741-743
Endemic pemphigus foliaceus (EPF) is an autoimmune disease characterized by blister formation with a loss of cohesion and infiltration of inflammatory cells. We observed that supernatants of peripheral blood mononuclear cells from patients produced significantly more interleukin-1beta (IL-1beta) than those from stimulated healthy controls. Furthermore, a Th2 bias was observed in EPF patients when the IL-5/gamma interferon ratio was analyzed. These results indicate that cells from pemphigus patients react with a vigorous proinflammatory response. 相似文献
35.
dos Santos CN Rocha CF Cordeiro M Fragoso SP Rey F Deubel V Desprès P 《Virus research》2002,90(1-2):197-205
We have investigated the genetic diversity of dengue type-1 (DEN-1) virus in Brazil. The full nucleotide sequences of three DEN-1 virus isolated from DEN fever (DF) and DEN hemorrhagic fever patients in northeastern Brazil in 1997 (BR/97) and one from a DF patient in the south of Brazil in 2001 (BR/01) were compared to that of the reference strain BR/90 obtained in the city of Rio de Janeiro in 1990. Sequence analysis showed that the structural proteins were remarkably conserved between all isolates. A total of 27 amino acid changes occurred throughout the non-structural proteins. Among them, nine amino acid substitutions were specific of BR/97 and BR/01 isolates, indicating that in situ evolution of these strains had occurred. Within the BR/97 and BR/01 samples, some amino acid substitutions have been previously identified in DEN-1 virus strains sequenced so far, suggesting that recombination events might have occurred. 相似文献
36.
Lima AP dos Reis FC Serveau C Lalmanach G Juliano L Ménard R Vernet T Thomas DY Storer AC Scharfstein J 《Molecular and biochemical parasitology》2001,114(1):41-52
Cysteine-proteinases from parasitic protozoa have been recently characterized as factors of virulence and pathogenicity in several human and veterinary diseases. In Chagas' disease, the chronic infection caused by Trypanosoma cruzi, structure-functional studies on cysteine proteases were thus far limited to the parasite's major isoform, a cathepsin L-like lysosomal protease designated as cruzipain, cruzain or GP57/51. Encoded by a large gene family, cruzipain is efficiently targeted by synthetic inhibitors, which prevent parasite intracellular growth and differentiation. We have previously demonstrated that the multicopy cruzipain gene family includes polymorphic sequences, which could encode functionally different isoforms. We report here a comparative kinetic study between cruzain, the archetype of the cruzipain family, and an isoform, termed cruzipain 2, which is expressed preferentially by the mammalian stages of T. cruzi. Heterologous expression of the catalytic domain of cruzipain 2 in Saccharomyces cerevisae yielded an enzyme that differs markedly from cruzain with respect to pH stability, substrate specificity and sensitivity to inhibition by natural and synthetic inhibitors of cysteine proteases. We suggest that the structural-functional diversification imparted by genetic polymorphism of cruzipain genes may have contributed to T. cruzi adaptation to vertebrate hosts. 相似文献
37.
do Valle Matta MA Sales Alviano D dos Santos Silva Couceiro JN Nazareth M Meirelles L Sales Alviano C Angluster J 《Parasitology research》1999,85(4):293-299
The cell-surface expression of sialoglycoconjugate structures in wild-type Crithidia fasciculata and its TFRR1 drug-resistant mutant was analyzed with the aid of an influenza C virus strain, lectin, enzymatic treatment, and flow cytofluorimetry
analysis probed with fluorescein isothiocyanate-labeled (FITC) lectins. 9-O-Acetyl-N-acetyl neuraminic acid (Neu5,9Ac2) structures mediate influenza C virus cell-binding. The SAα2,3Gal and SAα2,6Gal sequences are specifically recognized by
Maackia amurensis (MAA) and Sambucus nigra (SNA) lectins, respectively. On the basis of these param- eters the TFRR1 mutant strain of C. fasciculata was found to contain exposed sialoglycoconjugates bearing Neu5,9Ac2 surface structures. After the removal of sialic acid residues by neuraminidase activity the marked increases in PNA (peanut
agglutinin)-mediated agglutinating activity showed that those acidic units on C. fasciculata cells were glycosidically linked to d-galactose. The bond involves SAα2,6Gal and SAα2,3Gal linkages as suggested by the use of FITC-SNA and FITC-MAA lectins, respectively.
Both SAα2,3Gal and SAα2,6Gal sequences were preferentially expressed by the TFRR1 mutant. The SAα2,6 linkage markedly predominated. In the TFRR1 mutant, but not in wild-type cells, two distinct populations of cells were distinguished by reactivity with FITC-SNA, one
of which was enriched with surface SAα2,6Gal sequences. These diverse findings suggest that sialoglycoconjugate structures
present on the flagellate surface may be associated with mutation and the cell growth cycle in C. fasciculata.
Received: 17 September 1998 / Accepted: 22 October 1998 相似文献
38.
Nascimento Jdos S Giambiagi-deMarval M de Oliveira SS Ceotto H dos Santos KR Bastos Mdo C 《Research in microbiology》2005,156(8):837-842
Among 363 strains of Staphylococcus aureus, 21 were shown to produce bacteriocins (Bac), antimicrobial peptides with potential biotechnological applications. This collection includes strains which are either isolated from food, patients and healthy cattle, or are involved in subclinical bovine mastitis. From these 21 strains, 17 were shown to carry closely-related 8.0-kb Bac plasmids encoding bacteriocins either identical to or similar to aureocin A70, a bacteriocin able to inhibit strains of Listeria monocytogenes, a food-borne pathogen. Such findings prompted us to investigate the genetic relationships among these Bac+ strains. To obtain more discriminatory results, a combined analysis of AP-PCR, rep-PCR, and a modified PCR technique that we designated SD-PCR was employed. The 17 Bac+ strains harboring 8.0-kb Bac plasmids exhibited seven fingerprint patterns. One such genotype was composed of 8 out of the 11 strains associated with bovine mastitis, which suggests the prevalence of a clone of Bac+ strains involved in this animal infection carrying 8.0-kb Bac plasmids. Our data support the assumption that Bac+ strains of S. aureus carrying genetically related 8.0-kb Bac plasmids do not belong to a single clone. It seems, therefore, that 8.0-kb Bac plasmids have spread horizontally among different S. aureus strains. There also seems to be genetic diversity among the remaining Bac+ strains analyzed. 相似文献
39.
Castro NH dos Santos RC Nelson R Beçak W Hane B Lindsey CJ Lubs HA Stevenson RE Schwartz CE 《American journal of medical genetics. Part A》2003,(1):49-51
This report describes a family with mental retardation in two brothers. The pedigree is consistent with either X-linked mental retardation or autosomal recessive inheritance. The clinical features consist of coarse face, prominent lower lip, large testes, and obesity. This same constellation of findings was observed in a family with X-linked mental retardation (XLMR) reported by Shashi et al. [2000: Am J Hum Genet 66:469-479]. Furthermore, haplotype analysis was consistent with localization of the Shashi XLMR syndrome in Xq26-q27. Thus, the family likely represents a second occurrence of the Shashi XLMR syndrome. 相似文献
40.
Maria do Carmo Debur Juliano Bordignon Claudia Nunes Duarte dos Santos Luine Rosele Vidal Meri Bordignon Nogueira Sérgio Monteiro de Almeida Sonia Mara Raboni 《Journal of clinical virology》2007,39(1):59-62
BACKGROUND: Human metapneumovirus (hMPV) has been described as an etiologic agent of acute respiratory infections (ARI), mainly in pediatric patients. Viral isolation is difficult and has low sensitivity, and consequently RT-PCR assays are currently used for detection. OBJECTIVES: Detect hMPV in ARI in hospitalized children in Southern Brazil; standardize a RT-PCR for routine hMPV diagnosis; validate a positive control for molecular tests; and perform phylogenetics analyses. STUDY DESIGN: Nasopharyngeal aspirates (NPA) from 156 hospitalized children were studied. A conserved region of the nucleoprotein gene was cloned, characterized and used to standardize an RT-PCR assay. Phylogenetic analyses were performed. Clinical data were obtained from medical records. RESULTS: hMPV was detected in 6.4% of the samples. Dyspnea and wheezing were frequently reported symptoms and the most common diagnoses were bronchiolitis, acute respiratory insufficiency or laryngotracheobronchitis. Nucleotide sequence alignment revealed 97.7% identity with genotype A1 of hMPV. The detection limit of hMPV genomes by RT-PCR in clinical samples was 180 copies/microL. CONCLUSION: This is the first report of the detection and genetic characterization of hMPV infections in children with lower ARI in Southern Brazil. 相似文献