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91.
Olivier Verneau Frédéric Thomas Anne de Meeüs François Catzeflis François Renaud 《Parasitology research》1995,81(7):591-594
The genetic diversity of two samples of Cestoda (Bothriocephalus funiculus, Renaud and Gabrion, 1984) parasitizing two sympatric teleostean species was assessed using random amplified polymorphic DNA (RAPD). A total of 72Bothriocephalus were analyzed individually, and electrophoretic analysis of the amplification products of 65 primers among the 68 tested revealed monomorphic patterns, reflecting the close genetic relatedness within and between the parasites of the two samples. However, 3 primers showed polymorphic patterns at 6 RAPD sites. Analysis of the distribution of these genomic fragments, assuming random mating, showed strong linkage disequilibria (only 8 genetic combinations were observed among the 32 expected). Two genetic entities displaying a high degree of host specificity were evidence within our two samples ofB. funiculus. This powerful molecular technique can be used as a diagnostic tool in studies concerning the biodiversity of related genetic entities and could have broad applications in parasitology. 相似文献
92.
93.
Pajot A Pancré V Fazilleau N Michel ML Angyalosi G Ojcius DM Auriault C Lemonnier FA Lone YC 《International immunology》2004,16(9):1275-1282
Transgenic mice expressing human HLA class II molecules provide a useful model for identifying HLA-restricted CD4+ epitopes. However, the influence of endogenous murine H-2-restricted T cell responses on HLA-restricted responses is not known. In the present study, we show that HLA-DR1 transgenic mice deficient for H-2 class II expression (HLA-DR1+/+/IAbeta0/0) exhibit an equivalent expression level of the transgene HLA-DR1 and a similar diversity in the TCR repertoire, but a slightly different number of CD4+ peripheral T cells, when compared to HLA-DR1 transgenic mice in which H-2 class II molecules were retained (HLA-DR1+/+/IAbeta+/+). More importantly, a strong antigen-specific HLA-DR1-restricted response was observed in nearly all HLA-DR1+/+/IAbeta0/0 mice immunized with HBV envelope protein (HBs) or capsid protein (HBc), whereas weak HBs- or HBc-specific HLA-DR1-restricted responses were detected in half of the immunized HLA-DR1+/+/IAbeta+/+ mice. Conversely, strong HBs- or HBc-specific H-2-restricted T cell responses were detected in HLA-DR1+/+/IAbeta+/+ mice but not in HLA-DR1+/+/IAbeta0/0 mice. Our results indicate that the coexpression of endogenous H-2 class II molecules reduces the intensity of HLA-DR1-restricted antigen-specific responses in transgenic mice, by favoring murine over human MHC recognition and education. Thus, HLA-DR1+/+/IAbeta0/0 mice represent a better model for identifying and characterizing HLA-DR1-restricted epitopes relevant for human disease. 相似文献
94.
Daphné Lehalle Roberto Colombo Michael O'Grady Bénédicte Héron Nada Houcinat Paul Kuentz Sebastien Moutton Arthur Sorlin Julien Thevenon Julian Delanne Sebastien Gay Caroline Racine Aurore Garde Frédéric Tran Mau‐Them Christophe Philippe Antonio Vitobello Sophie Nambot Frédéric Huet Yannis Duffourd François Feillet Christel Thauvin‐Robinet Sandrine Marlin Laurence Faivre 《American journal of medical genetics. Part A》2019,179(9):1756-1763
Alpha‐mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi‐systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha‐mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha‐mannosidase in leucocytes and screening for abnormal urinary excretion of mannose‐rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDER) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3–23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two‐sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management. 相似文献
95.
Christelle Faveeuw Marie-Claude Gagnerault Fran?oise Lepault 《Clinical & developmental immunology》1994,3(4):273-282
Subpopulations of lymphoid cells were compared with respect to their ability to migrate into
peripheral lymphoid organs of nonobese diabetic (NOD) mice and various strains of control
mice. In short-term, in vivo homing studies, no major differences in the pattern of homing
of B and T cells were observed among all mouse strains studied. On the other hand, CD4
cells localized consistently more efficiently than CD8 cells in both PP and LN of adult NOD
and BALB/c mice, whereas both populations migrated roughly equivalently in LN of adult
DBA/2, CBA, and C57BL/6 mice. No age-dependent differences in the homing of CD4 and
CD8 cells were observed in BALB/c mice. On the contrary, in 2-week-old NOD mice, CD4
and CD8 cells migrated equally well. The preferential entry of CD4 cells in adult NOD and
BALB/c did not result from increased blood transit time of CD8 cells. On the other hand,
the preferential migration of CD8 cells was observed in the liver, whereas the two T-cell
subsets migrated equally well in the lungs. The differences in the homing characteristics of
CD4 and CD8 cells among NOD, BALB/c, and C57BL/6 mice were not related to
modifications in the level of expression of adhesion molecules such as MEL-14, LFA-1, and
Pgp-1. 相似文献
96.
Marie-Laure Muiras Marcus Müller François Schächter A. Bürkle 《Journal of molecular medicine (Berlin, Germany)》1998,76(5):346-354
Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins which is catalyzed by poly(ADP-ribose) polymerase
and represents an immediate response of eukaryotic cells to oxidative and other types of DNA damage. Previously a strong correlation
had been detected between maximal poly(ADP-ribose) polymerase activity in permeabilized mononuclear leukocytes of various
mammalian species and species-specific life span. To study a possible relation between longevity and poly(ADP-ribosyl)ation
in humans we measured maximal oligonucleotide-stimulated poly(ADP-ribose) polymerase activity in permeabilized, Epstein-Barr
virus transformed lymphoblastoid cell lines from a French population of 49 centenarians and 51 controls aged 20–70 years.
Maximal enzyme activity was significantly higher in centenarians than in controls [median of controls: 9035 cpm/106 cells (lower quartile: 6156; upper quartile: 11,410); median of centenarians: 10,380 cpm/106 cells (lower quartile: 7994; upper quartile: 12,991); P=0.031 by Mann-Whitney U test]. In a subset of 16 controls and 24 centenarians, cellular poly(ADP-ribose) polymerase content was determined by quantitative
western blotting, thus allowing the calculation of specific enzyme activity. The latter was significantly higher in centenarians
(P=0.006), the median value for centenarians being about 1.6-fold that of controls. Specific poly(ADP-ribose) polymerase activity
was a more powerful parameter for differentiating between centenarians and controls than enzyme activity relative to cell
number. In addition, in a genetic association study we analyzed 437 DNA samples (239 centenarians and 198 controls) by PCR
amplification of a polymorphic dinucleotide repeat located in the promoter region of the poly(ADP-ribose) polymerase gene
in an attempt to detect an association between this polymorphic marker and variability of enzyme activity or human longevity.
However, this genetic analysis revealed no significant enrichment of any of the alleles or genotypes identified among centenarians
or controls, but its power was limited by the relatively weak hetero-zygosity of this polymorphic marker in our population
(51%). Viewed together with previous results on poly(ADP-ribose) polymerase activity in various mammalian species, the present
data provide further evidence for the notion that longevity is associated with a high poly(ADP-ribosyl)ation capacity.
Received: 5 September 1997 / Accepted: 10 November 1997 相似文献
97.
Toussaint O Remacle J Dierick JF Pascal T Frippiat C Royer V Chainiaux F 《Mechanisms of ageing and development》2002,123(8):937-946
98.
Roberts ML Wells DJ Graham IR Fabb SA Hill VJ Duisit G Yuasa K Takeda S Cosset FL Dickson G 《Human molecular genetics》2002,11(15):1719-1730
The ability to transfer the dystrophin gene stably to the skeletal muscle of DMD patients is a major confounding issue in establishing an effective gene therapy for this disease. To overcome this problem, we have examined the ability of muscle fibres from mdx mice to act as in situ factories of retroviral vector production. Tibialis anterior (TA) muscles from 4-week-old mdx mice were injected with an adenoviral vector expressing LacZ within a retroviral expression cassette (AdLZIN). Retroviral vector production was induced by the inclusion of two additional adenoviral vectors expressing retroviral gag-pol (AdGagPol) and 10A1 env genes (Ad10A1). Upon introduction of infected muscles into cell culture, colonies of beta-galactosidase-expressing myotubes formed only in cultures where the muscle was injected with AdLZIN, AdGagPol and Ad10A1, but not from muscle injected with AdLZIN only. Muscles from mdx/nude mice producing retroviral vector displayed a 4.6-fold increase in beta-galactosidase-positive myofibres after 1 month, compared with contralateral muscle in the same animal injected with AdLZIN and AdGagPol only. By constructing a hybrid adeno-retroviral vector expressing a truncated micro-dystrophin construct (AdmicroDyIN), we were able to partially correct the mdx dystrophic phenotype. AdmicroDyIN-mediated expression of micro-dystrophin in mdx TA muscle restored the formation of the dystrophin-associated glycoprotein complex and significantly reduced the level of muscle degeneration over uninjected controls. By stimulating in situ production of retroviral vector expressing micro-dystrophin, we achieved 92%+/-6% transduction of myofibres in the TA muscle by 4 weeks. Strikingly, by 3 months post injection, micro-dystrophin was still expressed to high levels in nearly all the myofibres of the TA muscle. By comparison, there was a pronounced drop in the levels of micro-dystrophin expressed by muscles injected with AdmicroDyIN only. Finally, using a novel PCR approach, we detected reverse-transcribed, integrated proviral sequences in TA muscle genomic DNA by 4 weeks post injection, the levels of which were found to increase after 3 months. 相似文献
99.
Rapid detection of Candida albicans in clinical blood samples by using a TaqMan-based PCR assay 总被引:2,自引:0,他引:2 下载免费PDF全文
Maaroufi Y Heymans C De Bruyne JM Duchateau V Rodriguez-Villalobos H Aoun M Crokaert F 《Journal of clinical microbiology》2003,41(7):3293-3298
We describe a rapid and reproducible PCR assay for quantitation of the Candida albicans ribosomal DNA (rDNA) in clinical blood samples based on the TaqMan principle (Applied Biosystems), in which a signal is generated by cleavage of a template-specific probe during amplification. We used two fluorogenic probes based on universal, fungus-specific primers, one for the detection of C. albicans species DNA and one for the detection of all Candida genus DNA. C. albicans blastoconidia mixed with whole blood in a titration experiment yielded a linear PCR signal over a range of 3 orders of magnitude. The TaqMan-based PCR assay for C. albicans exhibited a low limit of detection (5 CFU/ml of blood) and an excellent reproducibility (96 to 99%). While the C. albicans species-specific probe had 100% specificity for C. albicans, all Candida genus-specific probes cross-reacted with other organisms likely to coinfect patients with C. albicans infections. On the basis of these data, we determined the C. albicans loads with a species-specific probe from 122 blood samples from 61 hematology or oncology patients with clinically proven or suspected systemic Candida infections. Eleven positive samples exhibited a wide range of C. albicans loads, extending from 5 to 100,475 CFU/ml of blood. The sensitivity and specificity of the present assay were 100 and 97%, respectively, compared with the results of blood culture. These data indicate that the TaqMan-based PCR assay for quantitation of C. albicans with a species-specific probe provides an attractive alternative for the identification and quantitation of C. albicans rDNA in pure cultures and blood samples. 相似文献
100.
de Pontual L Népote V Attié-Bitach T Al Halabiah H Trang H Elghouzzi V Levacher B Benihoud K Augé J Faure C Laudier B Vekemans M Munnich A Perricaudet M Guillemot F Gaultier C Lyonnet S Simonneau M Amiel J 《Human molecular genetics》2003,12(23):3173-3180
Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is a rare disorder of the chemical control of breathing. It is frequently associated with a broad spectrum of dysautonomic symptoms, suggesting the involvement of genes widely expressed in the autonomic nervous system. In particular, the HASH-1-PHOX2A-PHOX2B developmental cascade was proposed as a candidate pathway because it controls the development of neurons with a definitive or transient noradrenergic phenotype, upstream from the RET receptor tyrosine kinase and tyrosine hydroxylase. We recently showed that PHOX2B is the major CCHS locus, whose mutation accounts for 60% of cases. We also studied the proneural HASH-1 gene and identified a heterozygous nucleotide substitution in three CCHS patients. To analyze the functional consequences of HASH-1 mutations, we developed an in vitro model of noradrenergic differentiation in neuronal progenitors derived from the mouse vagal neural crest, reproducing in vitro the HASH-PHOX-RET pathway. All HASH-1 mutant alleles impaired noradrenergic neuronal development, when overexpressed from adenoviral constructs. Thus, HASH-1 mutations may contribute to the CCHS phenotype in rare cases, consistent with the view that the abnormal chemical control of breathing observed in CCHS patients is due to the impairment of noradrenergic neurons during early steps of brainstem development. 相似文献