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61.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
62.
Adrenergic and dopaminergic response to chronic chair restraint in the rhesus monkey. 总被引:4,自引:0,他引:4
Prolonged chair restraint and social isolation in the rhesus monkey led to a reduction in the urinary excretion of HVA (4-hydroxy-3-methoxyphenylacetic acid), DOPAC (3,4-dihydroxyphenylacetic acid), VMA methoxy-4-hydroxymandelic acid), and MHPG (3-methoxy-4-hydroxyphenylethylglycol) over a 3 week period. This adaptation to a chronically "stressful" situation corresponds to earlier studies on the rhesus monkey indicating a gradual reduction in the urinary excretion of norepinephrine and epinephrine after initiation of restraint. The following basic information on the urinary excretion of catecholamine metabolites was obtained: (1) the rate of excretion of the dopamine metabolites (HVA and DOPAC) is about four times higher than the rate of excretion of adrenergic metabolites (VMA and MHPG): (2) MHPG is the major adrenergic metabolite in the rhesus monkey; and (3) the excretion rates of the urinary metabolites varied considerably between animals. 相似文献
63.
Barbara Riond Marina L. Meli Ueli Braun Peter Deplazes Kaspar Joerger Rudolf Thoma Hans Lutz Regina Hofmann-Lehmann 《Comparative clinical pathology》2008,17(3):171-177
An outbreak of a fatal haemolytic anaemia in a dairy herd of cattle in Switzerland was shown to be associated with infections
with five vector-borne pathogens, namely Anaplasma marginale, A. phagocytophilum, Babesia bigemina, a Theileria spp belonging to the buffeli/sergenti/orientalis complex and haemotrophic Mycoplasma spp. The latter three had not been documented before this outbreak in Switzerland. To characterise the haematological and blood
chemical changes in these unique cows, packed cell volume was determined in all 286 blood samples, blood smears, and complete
haematology were performed from 285 and 173 blood samples, respectively, and biochemical parameters were assayed in 105 serum
samples. Regenerative anaemia was the key sign of illness. Red blood cells of anaemic cattle were hypochromic and macrocytic.
Anaemic animals had reduced platelet cell counts and increased total white cell counts. In addition, increased serum bilirubin,
blood aspartate aminotransferase, gamma glutamyltransferase, glutamic dehydrogenase and blood urea nitrogen and decreased
magnesium, calcium and albumin levels were found in anaemic cattle when compared to animals with normal packed cell volume.
Most changes could not be attributed to a single infection. A. marginale seemed to be important in causing the outbreak, but co-infections may have aggravated the disease development and clinical
signs. Thus, when encountering cattle with haemolytic anaemia, all of the mentioned pathogens should be included as differential
diagnosis. 相似文献
64.
65.
Ch. Ell J. Braun H. J. König S. Domschke W. Domschke 《Journal of molecular medicine (Berlin, Germany)》1985,63(12):572-574
Summary The pharmacokinetics of high-dose metoclopramide (10 mg/kg body wt. in five infusions of 2 mg/kg body wt. each) was studied in 11 patients (5 females, 6 males) in two groups: group A with and group B (consisting of five patients) without forced diuresis. When the drug was infused, forced diuresis had no influence on the pharmacokinetics of metoclopramide (serum level after the 1st infusion was 851±361 ng/ml in group A versus 840±348 ng/ml in group B; after the 5th infusion it was 2,005±588 ng/ml in group A versus 2,463±1,350 ng/ml in group B). There were significant differences in the 24-h serum levels (582±308 ng/ml in group A versus 379±170 ng/ml in group B;P<0.05) and in the elimination half life (8.5±2.6 h in group A versus 6.1±1.1 h in group B;P<0.05). The results demonstrate that the dosage regimen originally suggested by Gralla for cytostatic drugs, with forced diuresis for high-dose metoclopramide therapy, may also be applied, with no dosage reduction, with to other cytostatic drugs which do not require forced diuresis. 相似文献
66.
A. Braun 《Medical microbiology and immunology》1960,147(1):79-93
Zusammenfassung Es wird über Erfahrungen bei der Typenbestimmung von 127 Tuberkelbakterien-Stämmen berichtet, die aus menschlichen Untersuchungsstoffen (95), Organen perlsüchtiger Rinder (15) und Organen tuberkulöser Hühner (17) gezüchtet wurden. Zur Differenzierung zogen wir die kulturmorphologischen Eigenschaften, den Bromkresolpurpur-Nährboden (Wagener u.Mitscherlich), die Feststellung des O2-Bedarfes (Lebek), die Katalase-Aktivität (Middlebrook), den Niacin-Test (Bönicke u.Lisboa), die Testung gegenüber Brenzschleimsäurehydracid (Bönicke u.Lisboa) und Tierversuche heran. Schwierigkeiten entstanden nur bei fermentschwachen und isoniazid-resistenten Stämmen beider Säugetiertypen der Tuberkelbakterien. Dabei verhielt sich keines der Verfahren immer typengerecht. Die Typendiagnose kann also nur unter Auswertung mehrerer Methoden gewonnen werden.Auf den kürzlich vonBönicke empfohlenen Nicotinamidase-Test zur Identifizierung schwierig einzuordnender, auch isoniazidresistenter Stämme wurde hingewiesen.Der Brenzschleimsäurehydrazid-Test und die Methode der Prüfung des O2-Bedarfes eignen sich nach unseren Beobachtungen nicht für die Erkennung von Geflügeltuberkelbakterien. 相似文献
67.
Patient motion occurring during data acquisition in single photon emission computed tomography (SPET) can cause serious reconstruction artefacts. We have developed a new approach to correct for head motion in brain SPECT. Prior to motion, projections are assigned to conventional projections. When head motion occurs, it is measured by a motion monitoring system, and subsequent projection data are mapped to 'virtual' projections. The appropriate position of each virtual projection is determined by applying the converse of the patient's accumulated motion to the actual camera projection. Conventional and virtual projections, taken together, form a consistent set that can be reconstructed using a three-dimensional (3D) algorithm. The technique has been tested on a range of simulated rotational movements, both within and out of the transaxial plane. For all simulated movements, the motion corrected images exhibited better agreement with a motion free reconstruction than did the uncorrected images. This technique may help to overcome one of the major remaining limitations on image quality and quantitative accuracy in SPECT. 相似文献
68.
Boldogköi Zsolt Braun Attila Medveczky István Glávits Róbert Gyúró Bence Fodor István 《Virus genes》1998,17(1):89-98
A recombinant pseudorabies (Aujeszky’s disease) virus (PrV) designated as vE16lac was constructed by deleting a 3-kbp DNA
segment spanning the junction of long and short components of the viral genome, and by replacing the deleted segment with
a lacZ-expression cassette. The aim of constructing this mutant was (a) to determine whether the terminal repeat (Tr) can
serve as a template for the regeneration of the internal repeat (Ir), and (b) whether this deletion causes a reduction in
the neuroinvasiveness of the virus. To analyze the mechanism of equalization, revertant viruses were selected and structurally
characterized from vE16lac infection of PK-15 cells, mice and pigs. Because all revertants acquired Ir sequences identical
to that of the wild-type virus, the equalization process occurred using the Tr as a template to reconstitute the Ir. We also
found that the recombinant virus vE16lac was virulent in both pigs and mice. The data are discussed in view of studies performed
with similar PrV mutants by other authors (Rall et al., 1992, Dean and Cheung, 1995 and Dean et al., 1996).
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
69.
Andrzej Bedzki Henri Balard Dietrich Braun 《Macromolecular chemistry and physics.》1981,182(4):1057-1062
The telechelics 1 from methyl methacrylate and 1,1,2,2-tetraphenyl-1,2-diphenoxyethane, can be separated by adsorption chromatography. The structure of the dimers and trimers was identified by 1H NMR-spectroscopy. The free radical oligomerization is a process in which the syndiotactic structure is favoured above the isotactic one. 相似文献
70.
Integrin-linked kinase (ILK) is required for polarizing the epiblast,cell adhesion,and controlling actin accumulation 总被引:15,自引:0,他引:15 下载免费PDF全文
Sakai T Li S Docheva D Grashoff C Sakai K Kostka G Braun A Pfeifer A Yurchenco PD Fässler R 《Genes & development》2003,17(7):926-940
Integrin-mediated cell-matrix interactions are essential for development, tissue homeostasis, and repair. Upon ligand binding, integrins are recruited into focal adhesions (FAs). Integrin-linked kinase (ILK) is an FA component that interacts with the cytoplasmic domains of integrins, recruits adaptor proteins that link integrins to the actin cytoskeleton, and phosphorylates the serine/threonine kinases PKB/Akt and GSK-3beta. Here we show that mice lacking ILK expression die at the peri-implantation stage because they fail to polarize their epiblast and to cavitate. The impaired epiblast polarization is associated with abnormal F-actin accumulation at sites of integrin attachments to the basement membrane (BM) zone. Likewise, ILK-deficient fibroblasts showed abnormal F-actin aggregates associated with impaired cell spreading and delayed formation of stress fibers and FAs. Finally, ILK-deficient fibroblasts have diminished proliferation rates. However, insulin or PDGF treatment did not impair phosphorylation of PKB/Akt and GSK-3beta, indicating that the proliferation defect is not due to absent or reduced ILK-mediated phosphorylation of these substrates in vivo. Furthermore, expression of a mutant ILK lacking kinase activity and/or paxillin binding in ILK-deficient fibroblasts can rescue cell spreading, F-actin organization, FA formation, and proliferation. Altogether these data show that mammalian ILK modulates actin rearrangements at integrin-adhesion sites. 相似文献