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981.
A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts 总被引:3,自引:0,他引:3
982.
Francis MJ; Jones EE; Levy ER; Ponnambalam S; Chelly J; Monaco AP 《Human molecular genetics》1998,7(8):1245-1252
Menkes disease arises from a genetic impairment in copper transport. The
gene responsible for the phenotype has been identified as a copper
transporting ATPase ( ATP7A ). Recently, the protein encoded by the ATP7A
gene has been localized to the Golgi complex. In order to investigate the
role of the Menkes disease protein in copper transport, recombinant
constructs containing both the full-length open reading frame and an
alternatively spliced form have been successfully expressed and localized
in mammalian cells. Other studies of a patient with occipital horn
syndrome, an allelic variant of Menkes disease, have demonstrated that only
this alternatively spliced isoform and not the full-length form is
expressed in this patient. The milder form of this patient's phenotype
suggests that the alternatively spliced isoform has some functional role in
copper transport. In the present study the full-length recombinant Menkes
protein was shown by immunofluorescence to localize to the Golgi apparatus
and the alternatively spliced form, lacking sequences for transmembrane
domains 3 and 4 encoded by exon 10, was shown to localize to the
endoplasmic reticulum. Using sequences from exon 10 fused to a non-Golgi
reporter molecule, a 38 amino acid sequence containing transmembrane domain
3 of the Menkes protein was found to be sufficient for localization to the
Golgi complex. Therefore, the protein sequence encoded by exon 10 may be
responsible for this differential localization and both isoforms may be
required for comprehensive transport of copper within the cell.
相似文献
983.
Wanker EE; Rovira C; Scherzinger E; Hasenbank R; Walter S; Tait D; Colicelli J; Lehrach H 《Human molecular genetics》1997,6(3):487-495
We report the discovery of the huntingtin interacting protein I (HIP-I)
which binds specifically to the N-terminus of human huntingtin, both in the
two-hybrid screen and in in vitro binding experiments. For the interaction
in vivo, a protein region downstream of the polyglutamine stretch in
huntingtin is essential. The HIP1 cDNA isolated by the two- hybrid screen
encodes a 55 kDa fragment of a novel protein. Using an affinity-purified
polyclonal antibody raised against recombinant HIP-I, a protein of 116 kDa
was detected in brain extracts by Western blot analysis. The predicted
amino acid sequence of the HIP-I fragment exhibits significant similarity
to cytoskeleton proteins, suggesting that HIP-I and huntingtin play a
functional role in the cell filament networks. The HIP1 gene is
ubiquitously expressed in different brain regions at low level. HIP-I is
enriched in human brain but can also be detected in other human tissues as
well as in mouse brain. HIP-I and huntingtin behave almost identically
during subcellular fractionation and both proteins are enriched in the
membrane containing fractions.
相似文献
984.
985.
HIV/AIDS remains a substantial health threat to men who have sex with men. Although new HIV medications have provided great benefits for many HIV-positive individuals, they have done little to protect HIV-negative men. Consequently, changing one's sexual practices remains the most effective way to reduce risk for HIV. However, to develop an effective intervention for reducing HIV risk, it is important to fully understand risk behavior. In this article, we detail the essential elements for conducting an HIV risk assessment as well as those contextual factors that may support risk behaviors. Further, we discuss the importance of procuring an HIV test and the critical issues that may arise because of testing for HIV as well as the critical issues that may result from testing HIV-positive. Finally, we illustrate how we integrate an HIV health risk assessment into a clinical interview. 相似文献
986.
Pseudoleukemia in Down's syndrome. Analysis of immunophenotype and gene rearrangement 总被引:1,自引:0,他引:1
D R Domenico G J Dizikes A R Melnyk M L Bird C R Suarez H R Schumacher 《American journal of clinical pathology》1989,91(6):709-714
This report demonstrates a case of transient abnormal myelopoiesis (TAM) evolving in a patient with Down's syndrome. A diagnosis was established after the patient's blast cell count decreased considerably three weeks after the initial leukemic phase. The blast population in the authors' case expressed Leu-9 (CD7), 6D1, and TdT+. Cytochemistries showed some of the blast population to be peroxidase positive and Sudan black positive. Platelet peroxidase by electron microscopic examination showed some positive blasts. Therefore, surface markers and cytochemical studies in this case suggested an abnormal proliferation involving a pluripotential stem cell capable of expressing myeloid and lymphoid characteristics. Cytogenetics was performed at birth and showed 47,XY,+21/48,XY,+21,+mar, confirming the diagnosis of Down's syndrome. The origin of the chromosomal fragment was uncertain. It was of interest that during the remission phase of his pseudoleukemia there was a concomitant decrease in the extra chromosomal fragment. Immunoglobulin and T-cell antigen receptor gene rearrangement studies showed only germline patterns, indicating that the lymphoid cells in the blast population were not clonally expanded. Therefore, immunoglobulin and T-cell antigen receptor rearrangement analysis and immunophenotyping are extremely valuable techniques in distinguishing between TAM and acute lymphoblastic leukemia in patients with Down's syndrome. 相似文献
987.
Soler AP Gilliard G Xiong Y Knudsen KA Martin JL De Suarez CB Mota Gamboa JD Mosca W Zoppi LB 《Human pathology》2001,32(2):149-155
The expression of the neural cell adhesion molecule (NCAM) was studied in normal human myocardium and in Chagas' disease myocarditis. We found that NCAM is expressed in the conduction system as well as the myocardium in the fetal heart, but its expression is restricted to the conduction system and absent in the adult myocardium. Chagas' disease is an American endemic disease caused by the Trypanosoma cruzi parasite, which produces myocarditis and a blockade of the conduction system, resulting in cardiac dysfunction. We studied the expression of NCAM in paraffin-embedded human heart tissues from 34 autopsies of patients with Chagas' myocarditis and from murine and canine experimental acute Chagas' myocarditis, using a polyclonal anti-NCAM antibody and immunohistochemistry. Our results show a dramatic upregulation of NCAM expression in the intercalated discs of cardiomyocytes in acute and chronic Chagas' myocarditis. Surprisingly, the NCAM signal was detected in intracellular nests of amastigote forms of the parasite, within infected cardiomyocytes of human and experimental Chagas' myocarditis. In contrast, cardiac cell-cell adhesion proteins, N-cadherin and beta-catenin, were found in intercalated discs distorted by the infection but absent from the amastigote nests. Proteins reactive to several antibodies against NCAM were detected by Western immunoblotting in cultured T cruzi parasites and in trypomastigote forms of T cruzi extracted from the blood of infected mice. The upregulation of NCAM in Chagas' myocarditis and the expression of NCAM or a NCAM-like protein by T cruzi suggest that NCAM may act as a receptor for tissue targeting and cellular invasion by T cruzi in Chagas' disease. 相似文献
988.
H5ts125 and H5ts107 are temperature sensitive mutants of type 5 adenovirus in the structural gene for the DNA binding protein. Spontaneous, temperature-independent revertants of these mutants were isolated by growth in HeLa cells at 39°. Out of 30 independently isolated temperature-independent revertants grown in HeLa cells, two isolates were found to retain their temperature sensitive phenotype when grown or plaqued in 293 cells, which are a human cell line transformed by type 5 adenovirus. These two revertants represent a new class of host range temperature conditional mutants. It is suggested that these revertants arise by either a viral-encoded extragenic suppressor mutation or a second site intragenic mutation that recognizes cellular proteins in HeLa and 293 cells differently. 相似文献
989.
C Natali J L Curtis L Suarez E J Millman 《Journal of the National Medical Association》1991,83(5):434-438
The preliminary observation that heavy drinking and smoking produced oral mucosal changes consisting of splotchy areas of depigmentation surrounded by hyperpigmentation was tested. The study population was comprised of 52 patients from an alcohol detoxification ward, who were compared with 54 patients from psychiatric inpatient and day hospital services. Structured interviewing was developed for both samples of patients who met either diagnostic criteria for alcohol abuse or dependence, or criteria for alcoholism on the Short Form of the Michigan Alcohol Screening Test, and were identified as nonsmokers or as those who smoked one to three or more packs of cigarettes a day. Photographs of the inner surface of the lips, oral mucosa, and gingivae independently were rated for severity of oral pigment change by two raters blind to a patient's alcohol or smoking history. This study demonstrates that reported observable oral pigment changes identify patients who are heavy smokers and drinkers, and may be a useful diagnostic sign. 相似文献
990.
Investigation of folate pathway gene polymorphisms and the incidence of neural tube defects in a Texas hispanic population 总被引:6,自引:0,他引:6
Barber R Shalat S Hendricks K Joggerst B Larsen R Suarez L Finnell R 《Molecular genetics and metabolism》2000,70(1):45-52
Neural tube defects (NTDs) are multifactorial in their etiology, having both genetic and environmental factors contributing to their development. Recent evidence demonstrates that periconceptional supplementation of the maternal diet with a multivitamin containing folic acid significantly reduces the occurrence and recurrence risk for having a pregnancy complicated by NTDs. Unfortunately, the mechanism underlying the beneficial effects of folic acid remains unknown. NTD surveillance data from the Texas-Mexico border show that the high NTD rate (28/10,000 live births) noted during the 1990-1991 Cameron county NTD cluster was superimposed on a background Cameron county NTD rate (16/10,000 live births) which is considerably higher than that generally noted in the United States (8-10/10,000 live births). These data suggest that genetic factors as well as transient environmental factors may contribute to the etiology of the NTDs. Furthermore, clinical and experimental evidence imply that allelic forms of genes involved with folate metabolism and/or transport may explain some of the observed variation in the NTD rates found across different populations. Two folate pathway genes were selected for evaluation in this study. The loci investigated included two known alleles of the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene, as well as the promoter region of the folate receptor-alpha (FR-alpha) gene. Odds ratios (ORs) for the C677T polymorphism in the MTHFR gene were 1.8 (CI 0.47-6.8) for heterozygosity and 1.8 (CI 0.35-9.4) for homozygosity for the mutant 677T allele, relative to wildtype homozygotes. The odds ratio for the heterozygosity for the A1298C polymorphism in the same gene was 1.1 (CI 0.09-14). No individuals homozygous for the 1298C allele were observed. The OR for heterozygosity of FR-alpha gene polymorphisms detected at nucleotide 762 and at nucleotides 610/631 was 1.4 and 0.7, respectively. Neither of the FR-alpha polymorphisms was observed in the homozygous condition. No statistically significant associations were observed for any of the polymorphisms examined, as the 95% confidence intervals for all of the ORs included one. However, the frequency of the MTHFR 677T allele in the largely Hispanic control group from Texas was significantly different from other populations (P < 0.005), and among the highest reported for any control populations examined. 相似文献