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101.
D'Adamo P Welzl H Papadimitriou S Raffaele di Barletta M Tiveron C Tatangelo L Pozzi L Chapman PF Knevett SG Ramsay MF Valtorta F Leoni C Menegon A Wolfer DP Lipp HP Toniolo D 《Human molecular genetics》2002,11(21):2567-2580
Non-specific mental retardation (NSMR) is a common human disorder characterized by mental handicap as the only clinical symptom. Among the recently identified MR genes is GDI1, which encodes alpha Gdi, one of the proteins controlling the activity of the small GTPases of the Rab family in vesicle fusion and intracellular trafficking. We report the cognitive and behavioral characterization of mice carrying a deletion of Gdi1. The Gdi1-deficient mice are fertile and anatomically normal. They appear normal also in many tasks to assess spatial and episodic memory and emotional behavior. Gdi1-deficient mice are impaired in tasks requiring formation of short-term temporal associations, suggesting a defect in short-term memory. In addition, they show lowered aggression and altered social behavior. In mice, as in humans, lack of Gdi1 spares most central nervous system functions and preferentially impairs only a few forebrain functions required to form temporal associations. The general similarity to human mental retardation is striking, and suggests that the Gdi1 mutants may provide insights into the human defect and into the molecular mechanisms important for development of cognitive functions. 相似文献
102.
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
103.
Ageing and genetic control of immune responsiveness 总被引:2,自引:0,他引:2
Ageing is associated with a progressive decline of immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena [1,2]. Many studies have been focussed on the mechanisms of the immunologic features of ageing. Alterations in cellular components of the immune system rather than in the extracellular milieu seem to account for most of the variations of immune competence in ageing [3]. 相似文献
104.
105.
G. Benga T. Borza H. Matei P. Hodor L. Frenţescu I. Ghiran C. Lupşe 《Comparative clinical pathology》1995,5(2):106-111
The diffusional water permeability (P d) of adult, pregnant female and fetal guinea-pig red blood cells (RBCs) was measured by a doping nuclear magnetic resonance (NMR) technique on control cells and following inhibition withp-chloromercuribenzene sulphonate (PCMBS). The values ofP d were around 5.0 × 10?3 cm/s at 15 °C, 5.3 × 10-3 cm/s at 20 °C, 6.6 × 10?3 cm/s at 25 °C, 7.5 × 10?3 cm/s at 30 °C and 8.6 × 10?3 cm/s at 37 °C with no significant differences between adult, pregnant female and fetal RBCs. Systematic studies on the effects of PCMBS on water diffusion indicated that the maximal inhibition was reached in 10 min at 37 °C with 0.1 mm PCMBS. The values of maximal inhibition ranged from 70%–77% at 15–30 °C to 57%–63% at 37 °C in the case of adult and from 64%–67% at 15–30 °C to 51% at 37 °C in the case of fetal RBCs. The basal permeability to water was estimated at 1.1 × 10?3 cm/s at 15 °C ,1.3 × 10?3 cm/s at 20 °C, 1.6 × 10?3 cm/s at 25 °C, 2.2 × 10?3 cm/s at 30 °C and 3.2 × 10?3 cm/s at 37 °C for adult and slightly higher values for fetal guinea pig RBCs as 1.6 × 10?3 cm/s at 15 °C, 2.0 × 10?3 cm/s at 20 °C, 2.4 × 10?3 cm/s at 25 °C, 2.6 × 10?3 cm/s at 30 °C and 4.2 × 10?3 cm/s at 37 °C. The activation energy of water diffusion was around 22 kJ/ mol, with no significant differences between the adult pregnant female and fetal RBCs, and increased to about 40 kJ/mol in the case of adult and pregnant RBCs and 34 kJ/mol for fetal RBCs after incubation with PCMBS in conditions of maximal inhibition of water diffusion. The membrane polypeptide electrophoretic pattern of adult and fetal guinea-pig RBCs was compared with its human counterpart. The guinea-pig membrane contained higher amounts of spectrin (band 1 and 2), whereas the proteins in bands 4.1, 4.2 and 6 were present in lower amounts. Considerable differences in polypeptides migrating in the region of bands 7 and 8 and in front of them were apparent between the two sources of RBC membranes where some bands were present only in the guinea-pig RBC membranes. The adult guinea-pig membranes contained smaller amounts of proteins migrating in band 4.5 and lacked band 8. 相似文献
106.
We have studied 50 Caucasoid children under 7 years of age with Haemophilus influenzae b disease. Half of the patients (Group A) had invasive disease shown by positive blood and/or spinal fluid culture. The other half (Group B) had noninvasive disease characterized by fever, nasopharyngitis, negative blood culture, and positive throat culture. Age, number of other siblings under 12 years old in the family, immune response, antibody production and genetic markers were compared in the two groups. Significant difference between the two groups was only seen in their genetic markers. HLA-B12 was present in 52% of Group A patients as opposed to 16% in Group B patients (P less than .01). HLA-Bw40 was present in 24% of group B patients and absent in all Group A patients (P less than .01). These findings would suggest that susceptibility and resistance towards developing invasive type b disease may be genetically determined. 相似文献
107.
Pietro Cavalli Daniela Giardino Giulietta Gottardi Federica Natacci Salvatore Savasta Lidia Larizza 《American journal of medical genetics. Part A》2001,104(2):157-164
We describe the case of a 15‐year‐old girl with multiple congenital anomalies, dysmorphic features, severe kyphoscoliosis, growth and mental retardation, and the absence of speech, in whom 35% of the cells carried a supernumerary ring chromosome 1. Fluorescence in situ hybridization (FISH) analysis using YAC/BAC clones spanning the region from 1p13 to 1q21 made it possible to determine the genomic content and structure of the ring(1), which was found to consist of the cytogenetic bands 1q21–22. A complex structure was delineated in the ring chromosome with a partial inverted duplication delimited by markers WI‐7732 and WI‐607, with WI‐7396 and WI‐8386 being the boundaries of the single copy segment. Comparison of the clinical signs of other patients with mosaic r(1) reported in the literature allowed the identification of a patient sharing a number of clinical signs including cataracts. Given that mutations of the GJA8 gene encoding connexin 50 (Cx50) and mapping to 1q21 have been associated with the presence of cataracts, it is possible that a gain in copy number or a rearrangement of GJA8 may contribute to cataractogenesis. 相似文献
108.
Krüger S Bier A Plaschke J Höhl R Aust DE Kreuz FR Pistorius SR Saeger HD Rothhammer V Al-Taie O Schackert HK 《Human mutation》2004,24(4):351-352
Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common hereditary cancer-susceptibility syndromes. Germline mutations in mismatch repair genes are associated with the clinical phenotype of HNPCC. We report ten novel germline mutations, three in MSH2 and seven in MLH1. All but one mutation have been found in families fulfilling criteria of the Bethesda guidelines; four of them additionally fulfilled the Amsterdam criteria I or II. Eight mutations were considered pathogenic and predictive diagnostics in healthy family members at risk shall be undertaken; these include five frameshift mutations leading to premature stop codons, in MSH2: c.1672delT (p.S558Xfs) and c.2466_2467delTG (p.C822X) and in MLH1: c.1023delG (p.R341Xfs), c.1127_1128dupAT (p.K377Xfs) and c.1310delC (p.P437Xfs); three mutations leading to splice aberrations, in MSH2: c.1661G>C (r.1511_1661del) and in MLH1: c.677+3A>C (r.589_677del) and c.1990-2A>G predicted to result in a splice site defect. The remaining two mutations are unclassified variants with assumed pathogenicity: one missense mutation in the highly conserved ATPase domain of MLH1 (c.122A>G [p.D41G]) and one in-frame insertion of twelve nucleotides in MLH1 (c.2155_2156insATGTGTTCCACA [p.I719delinsNVFHI]). These two mutations were not found in 102 alleles of healthy control individuals. The corresponding tumors from all patients showed a high level of microsatellite instability (MSI-H). Immunohistochemistry (IHC) revealed complete loss of expression of the affected protein in the tumor cells from all but three patients. The tumors from the patients with the mutations c.1127_1128dupAT and c.1990-2A>G showed a reduction of expression of the MLH1-protein, rather than complete loss. In the tumor from the patient with the missense mutation c.122A>G [p.D41G] a normal expression of the proteins coded by MLH1 and MSH2 was noticed. 相似文献
109.
Stefania Barozzi Daniela Soi Elisabetta Intieri Marisa Giani Mirko Aldè Eleonora Tonon Lia Signorini Alessandra Renieri Chiara Fallerini Paola Perin Giovanni Montini Umberto Ambrosetti 《American journal of medical genetics. Part A》2020,182(10):2345-2358
Alport syndrome (AS) is caused by mutations in collagen IV, which is widespread in the basement membranes of many organs, including the kidneys, eyes, and ears. Whereas the effects of collagen IV changes in the cochlea are well known, no changes have been described in the posterior labyrinth. The aim of this study was to investigate both the auditory and the vestibular function of a group of individuals with AS. Seventeen patients, aged 9–52, underwent audiological tests including pure‐tone and speech audiometry, immittance test and otoacoustic emissions and vestibular tests including video head impulse test, rotatory test, and vestibular evoked myogenic potentials. Hearing loss affected 25% of the males and 27.3% of the females with X‐linked AS. It was sensorineural with a cochlear localization and a variable severity. 50% of the males and 45.4% of the females had a hearing impairment in the high‐frequency range. Otoacoustic emissions were absent in about one‐third of the individuals. A peripheral vestibular dysfunction was present in 75% of the males and 45.4% of the females, with no complaints of vertigo or dizziness. The vestibular impairment was compensated and the vestibulo‐ocular reflex asymmetry was more evident in rotatory tests carried out at lower than higher speeds; a vestibular hypofunction was present in all hearing impaired ears although it was also found in subjects with normal hearing. A posterior labyrinth injury should be hypothesized in AS even when the patient does not manifest hearing disorders or evident signs of renal failure. 相似文献
110.
Lorenzo Moretta Guido Ferlazzo Cristina Bottino Massimo Vitale Daniela Pende Maria Cristina Mingari Alessandro Moretta 《Immunological reviews》2006,214(1):219-228
Summary: The different cell types of the innate immune system can interact with each other and influence the quality and strength of an immune response. The cross talk between natural killer (NK) cells and myeloid dendritic cells (DCs) leads to NK cell activation and DC maturation. Activated NK cells are capable of killing DCs that fail to undergo proper maturation ('DC editing'). Encounters between NK cells and DCs occur in both inflamed peripheral tissues and lymph nodes, where both cell types are recruited by chemokines released in the early phases of inflammatory responses. Different NK cell subsets (CD56bright CD16− versus CD56+ CD16+ ) differ in their homing capabilities. In particular, CD56bright CD16− NK cells largely predominate the lymph nodes. In addition, these two subsets display major functional differences in their cytolytic activity, cytokine production, and ability to undergo proliferation. NK cell functions are also greatly influenced by the presence of polarizing cytokines such as interleukin (IL)-12 and IL-4. The cytokine microenvironment reflects the presence of different cell types that secrete such cytokines in response to microbial products acting on different Toll-like receptors (TLRs). Moreover, NK cells themselves can respond directly to microbial products by means of TLR3 and TLR9. Thus, it appears that the final outcome of a response to microbial infection may greatly vary as a result of the interactions occurring between different pathogen-derived products and different cell types of the innate immunity system. These interactions also determine the quality and strength of the subsequent adaptive responses. Remarkably, NK cells appear to play a key role in this complex network. 相似文献