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101.
Bischoff FZ Sinacori MK Dang DD Marquez-Do D Horne C Lewis DE Simpson JL 《Human reproduction update》2002,8(6):493-500
Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development. 相似文献
102.
Seroprevalence of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 in several regions of Italy 总被引:2,自引:0,他引:2
Calabrò ML Sheldon J Favero A Simpson GR Fiore JR Gomes E Angarano G Chieco-Bianchi L Schulz TF 《Journal of human virology》1998,1(3):207-213
OBJECTIVE: To study the seroprevalence of Kaposi's sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV-8) in 779 Italian blood donors. STUDY DESIGN/METHODS: Sera were tested for antibodies to a latency-associated nuclear antigen (LANA) and a capsid related protein encoded by ORF65. RESULTS: Among all Italian donors, 17.7% and 18.7% had antibodies to LANA and ORF65 protein, respectively, and 24.1% had antibodies to at least one antigen. KSHV/HHV-8 seroprevalence was higher in the Po valley and in Sardinia than close to the sub-Alpine Veneto region, Tuscany, or Apulia. KSHV/HHV-8 seroprevalence was almost equally distributed between men and women but increased in the older age groups. CONCLUSIONS: The regional differences and age distribution in seroprevalence agree partially with the incidence of classic KS in Italy. The rarity of classic KS in KSHV/HHV-8-infected subjects and the equal gender distribution of seroprevalence suggest that other cofactors may contribute to KS development in human immunodeficiency virus type 1 (HIV-1)-uninfected individuals. 相似文献
103.
We have stratified the cancer risk implications of lobular pattern in situ neoplasias of the breast by separating marked examples of this histologic spectrum (lobular carcinoma in situ [LCIS]) from lesser examples (atypical lobular hyperplasia). The lesser-developed examples have been shown previously to have a lower relative risk (RR) of later invasive carcinoma of the breast (IBC). Forty-eight examples of LCIS were found in 10,542 otherwise benign breast biopsies, representing an incidence of 0.5%. Nine patients were excluded from follow-up because of bilateral mastectomy within 6 months of entry biopsy, IBC within 6 months of entry biopsy, or prior IBC. Follow-up of the remaining 39 patients was complete, averaged 18 years, and revealed an RR of subsequent IBC of 6.9 (P less than .00001). Average overall follow-up for LCIS patients was 19 years; it was 25 years for those alive and free of IBC at the time of their follow-up interview. Neither family history of IBC nor postmenopausal estrogen therapy further affected risk. The absolute risk of IBC after LCIS was 17% at 15 years (adjusted for withdrawals), and the RR was 8.0 in the first 15 years of follow-up compared with the general population. An analysis based on a time-dependent hazards model found that during the first 15 years following biopsy women with LCIS had 10.8 times the risk of breast cancer compared with biopsied women of comparable age who lacked proliferative disease. Some previously published articles reporting lobular neoplasia (LN) suggest that those series with the greatest incidences of LN (whether termed LN or LCIS) have the lowest RR of subsequent breast cancer. Those series with higher incidences of LN include less well-developed histologic patterns of LN (atypical lobular hyperplasia). We conclude that our study of LN and studies performed by others support the higher risk of IBC after histologically flagrant examples (LCIS, about nine times higher) and a relatively lower but definable risk after more histologically subtle examples (atypical lobular hyperplasia, four to five times lower). This relative cancer risk is probably not constant over more than 15 years; thus, cancer risk 15 to 25 years after initial diagnosis of LCIS is uncertain. 相似文献
104.
Human granulocyte-macrophage colony-stimulating factor (hGM-CSF): identification of a binding site for a neutralizing antibody. 总被引:2,自引:0,他引:2
E Nice P Dempsey J Layton G Morstyn D F Cui R Simpson L Fabri A Burgess 《Growth factors (Chur, Switzerland)》1990,3(2):159-169
One approach to the localization of functionally active regions of human granulocyte-macrophage colony-stimulating factor (hGM-CSF) is to map the epitopes recognized by neutralizing anti-hGM-CSF monoclonal antibodies. We have defined the epitope recognized by one neutralizing antibody (LMM102) using proteolytic fragments obtained by enzymic digestion of bacterially synthesized hGM-CSF. RP-HPLC fractionation of a tryptic digest resulted in the identification of an immunoreactive "tryptic core" peptide containing 66 amino acids (52% of the protein). Further digestion of this "tryptic core" with S. aureus V8 protease produced a unique immunoreactive hGM-CSF product comprising two peptides, residues 86-93 and 112-127, linked by a disulfide bond between residues 88 and 121. The individual peptides, generated by reduction with dithiothreitol, were not recognized by the antibody. An analog of this peptide has been synthesized chemically and shown to have similar immunoreactivity to the epitope obtained by enzymic digestion. A series of modified peptides has also been synthesized to identify further the region required for antibody recognition. 相似文献
105.
D Pollard-Knight E Hawkins D Yeung D P Pashby M Simpson A McDougall P Buckle S A Charles 《Annales de biologie clinique》1990,48(9):642-646
A technique based on surface plasmon resonance is described which can be used to detect changes of refractive index that occur when one partner of a molecular binding pair diffuses from solution to bind the other partner which is immobilised on a silver surface. Results for the molecular binding pairs; protein-antibody, hapten-antibody and DNA-DNA are described. Instrumentation necessary for implementation of the technique is detailed. Immunoassay of proteins and haptens is possible in less than one minute with a sensitivity of 10(-9) mol/l. Hybridisation of 10 fmoles of a 97 base target sequence on the 1 mm2 area of detection to an immobilised oligonucleotide probe can be detected in less than five minutes. Advantages of the technique include the ability to record the kinetics of binding reactions in "real time" and the lack of labels in this simple assay format. Methods of improving the sensitivity are discussed. 相似文献
106.
Partial characterization of the enzymatic activity associated with the binary toxin (type C2) produced by Clostridium botulinum. 总被引:2,自引:0,他引:2 下载免费PDF全文
Clostridium botulinum produces a binary toxin that possesses a heavy chain (approximately 100,000 daltons) and a light chain (approximately 50,000 daltons). The heavy chain is a binding component that directs the toxin to vulnerable cells, and the light chain is an enzyme that has mono(ADP-ribosyl)ating activity. A number of experiments have been done to help characterize the enzymatic activity of the toxin. The data reveal that the enzyme has a pH optimum within the range of 7.0 to 8.0. It is not inhibited or stimulated by physiological concentrations of sodium, potassium, calcium, or magnesium. The enzyme is inhibited by high concentrations of salt, however, as well as high concentrations of nicotinamide, thymidine, theophylline, and histamine; and it is stimulated by histone and lysolecithin. Boiling irreversibly denatures the light chain of the toxin, but denaturation caused by guanidine and urea is substantially reversible. Enzymatic activity is not altered by short exposure to lysosomal proteases, including cathepsin B, cathepsin H, dipeptidyl aminopeptidase, and catheptic carboxypeptidase B. 相似文献
107.
Elizabeth Billington Jane Simpson Jen Unwin Dominic Bray David Giles 《British journal of health psychology》2008,13(4):683-699
Objectives Hope is important in determining positive outcomes in a range of chronic illnesses. This study examined the role of hope in adjustment to end‐stage renal failure (ESRF) and consequent dialysis. Design A cross‐sectional design examined the ability of hope to predict adjustment to ESRF over and above other relevant variables. Methods Individuals receiving dialysis at 4 units in the North‐West UK were invited to take part in the study. 103 questionnaire packs were included in the analysis. Multiple regression equations determined whether hope was able to predict significant variance in adjustment over and above that accounted for by other factors (demographic and illness‐related factors, perceived control, and social support). Measures of anxiety, depression, and quality of life constituted a multidimensional measure of adjustment to ESRF. Results Each of the regression models was significant. Hope emerged as an independent significant predictor in five of the multiple regressions: anxiety; depression; effects and symptoms of kidney disease; and mental health quality of life. Age also emerged as an important predictor of outcome. Conclusions It appears that hope is a significant predictor of adjustment to ESRF. Clinical implications of this research are discussed, along with suggestions for future research. 相似文献
108.
Heritability and molecular genetic studies of endometriosis 总被引:22,自引:0,他引:22
Endometriosis is a common disease defined as the growth of endometrial tissue outside the uterine cavity that often results in a vast array of gynaecological problems including dyspareunia, dysmenorrhoea, pelvic pain and infertility. Despite the increasing evidence that supports a genetic component to this common gynaecological condition, the basic aetiology and pathogenesis of endometriosis remain unknown. It is likely that endometriosis is a common polygenic/multifactorial disease caused by an interaction between multiple genes as well as the environment. Such conditions do not have a clear Mendelian pattern of inheritance. Recent molecular cytogenetic studies on endometriotic tissue and an established endometriosis-derived cell line provide novel evidence that acquired chromosome-specific alterations may be involved in endometriosis, possibly reflecting clonal expansion of chromosomally abnormal cells. Molecular DNA studies examining the role of loss of heterozygosity in endometriotic lesions has identified candidate tumour suppressor gene loci, including 5q, 6q, 9p, 11q and 22q, that may play a role in the malignant transformation of endometriotic implants to endometrioid ovarian cancers. Evidence of mutations in the tumour suppressor PTEN gene in the endometrioid subtype of epithelial ovarian cancer further suggests that somatic genetic alterations represent early events in the transformation of benign endometriotic cells. Genetic factors are also likely to influence individual susceptibility to endometriosis. There is now evidence that heritable allelic differences in drug-metabolizing enzymes play an important role in the development of endometriosis. Further studies are warranted to identify major susceptibility gene(s) and the mechanism involved in endometriosis to assist in the development of better methods for early detection, diagnosis and prevention. 相似文献
109.
110.
Angela Simpson Karla Arruda Martin Chapman 《Clinical reviews in allergy & immunology》1997,15(4):461-469
Conclusions Asthma can occur as a result of allergy to both house dust mites and to storage mites. Many people worldwide are exposed to
more than one mite species in the domestic environment. The most common domestic mites areD. pteronyssinus, D. farinae, E. maynei, andB. tropicalis; other storage mites are found in homes much less frequently, even in tropical climates. Because of the ready availability
of allergen extracts for skin testing and immunotherapy, patients with respiratory symptoms are generally evaluated for sensitization
toD. pteronyssinus andD. farinae only. The evidence reviewed here suggests, however, that, although there are crossreactive allergens between many mite species,
most species have specific allergens that can be an important cause of IgE responses. Therefore, the role ofB. tropicalis andE. maynei in the etiology of asthma merits further investigation. Identification of species-specific and crossreactive allergens and
production of recombinant allergens would be useful tools in allergy practice. By skin-testing patients, physicians would
then be able to evaluate whether patients recognize crossreactive allergens or species-specific allergens and whether or not
there is a need for immunotherapy to more than one mite species. 相似文献