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31.
Braverman N Chen L Lin P Obie C Steel G Douglas P Chakraborty PK Clarke JT Boneh A Moser A Moser H Valle D 《Human mutation》2002,20(4):284-297
PEX7 encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Mutations in PEX7 cause rhizomelic chondrodysplasia punctata (RCDP), a distinct peroxisome biogenesis disorder. In previous work we described three novel PEX7 mutant alleles, including one, L292X, with a high frequency due to a founder effect. We have now extended our analysis to 60 RCDP probands and identified a total of 24 PEX7 alleles, accounting for 95% of the mutant PEX7 genes in our sample. Of these, 50% are L292X, 13% are IVS9+1G>C, and the remainder are mostly private. IVS9+1G>C occurs on at least three different haplotypes and thus appears to result from recurrent mutation. The phenotypic spectrum of RCDP is broader than commonly recognized and includes minimally affected individuals at the mild end of the spectrum. To relate PEX7 genotype and phenotype, we evaluated the consequence of the disease mutation on PEX7 RNA by Northern analysis and RT/PCR. We evaluated the function of the encoded Pex7 protein (Pex7p) by expressing selected alleles in fibroblasts from RCDP patients and assaying their ability to restore import of a PTS2 marker protein. We find that residual activity of mutant Pex7p and reduced amounts of normal Pex7p are associated with milder and variant phenotypes. 相似文献
32.
Molecular cloning, sequencing, and identification of a metalloprotease gene from Listeria monocytogenes that is species specific and physically linked to the listeriolysin gene. 总被引:24,自引:15,他引:24 下载免费PDF全文
The entire nucleotide sequence of an open reading frame located immediately downstream of the listeriolysin gene from a virulent Listeria monocytogenes serotype 1/2a strain was determined. The product of the open reading frame was 510 amino acids with a predicted molecular weight of 57,400. The deduced amino acid sequence of this open reading frame is highly similar to that of a family of secreted metalloproteases produced by various members of the genus Bacillus, of which thermolysin is the prototype. Immunoblots performed with specific antisera raised against thermolysin from Bacillus stearothermophilus allowed the detection of a 60-kDa polypeptide, corresponding to the pro-form of the protease, in culture supernatants of L. monocytogenes strains. In maxicell experiments, Escherichia coli recombinants harboring this open reading frame also specifically directed production of a 60-kDa protein. Protease activity was low to undetectable in both Listeria strains and E. coli recombinants. This is due to lack of processing of the inactive pro-form of the protease to its mature active form in both species. We have designated this gene mpl for metalloprotease of L. monocytogenes. The gene was present only in pathogenic L. monocytogenes strains, in which it was physically linked to the listeriolysin gene. 相似文献
33.
Barbashina V Heller DS Hameed M Albanese E Goldstein M Dashefsky B Dieudonne A Chakraborty R 《Virchows Archiv : an international journal of pathology》2000,436(2):138-139
Smooth-muscle neoplasms are rarely located in the spleen. They have been previously reported in five cases of children with
human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS). Two cases of children with HIV infection/AIDS
with autopsy and surgical pathology evidence of multiple smooth-muscle neoplasms with splenic involvement are presented. DNA
was extracted from histology slides in both cases for analysis for Epstein Barr (EB) virus. In both cases, the presence of
EB virus was confirmed. This paper documents two additional cases of the unusual phenomenon of splenic involvement by smooth-muscle
neoplasms in the setting of AIDS in childhood and further supports the role of EB virus in the development of these neoplasms.
Received: 27 January 1999 / Accepted: 23 August 1999 相似文献
34.
Nathan LM Nerlander LM Dixon JR Ripley RM Barnabas R Wholeben BE Musoke R Palakudy T D'Agostino A Chakraborty R 《Journal of acquired immune deficiency syndromes (1999)》2003,34(2):237-241
OBJECTIVE: As a result of the HIV epidemic in Africa, much debate exists on whether institutionalized compared with community-based care provides optimum management of infected children. Previous reports calculated 89% mortality by age 3 years among outpatients in Malawi. No similar data are available for infected children in institutionalized care. We characterized patterns of morbidity and mortality among HIV-1-infected children residing at an orphanage in Nairobi. METHODS: Medical records for 174 children followed over 5 years were reviewed. Mortality was analyzed by Kaplan-Meier methods with adjustment to account for survival in the community before admission. Anthropometric indices were calculated to include mean z scores for weight for length and length for age. Low indices reflected wasting and stunting. Opportunistic infections were documented. RESULTS: Of 174 children, 64 had died. Survival was 70% at age 3 years. Morbidity included recurrent respiratory tract infections, gastroenteritis, parotitis, and lymphoid interstitial pneumonitis. No new cases of tuberculosis disease were noted after admission. Mean z scores for length for age suggested overall stunting (z = -1.65). Wasting was not observed (z = -0.39). CONCLUSION: The optimal form of care for HIV-infected children in resource-poor settings may be the development of similar homes. Absence of tuberculosis disease in long-standing residents may have contributed to improved survival. Stunting in the absence of wasting implied that growth was compromised by opportunistic infections and other cofactors. 相似文献
35.
Temperature-sensitive mutants of reovirus type 3 are capable of interfering with the replication of wild-type reovirus type 3. The interfering activity correlated with the ability of pairs of mutants to complement at 39°: Pairs of noninterfering mutants (tsD × tsE) yielded efficient complementation (indexes of 10–50); pairs of interfering mutants (including members of groups ts A, B, G) did not produce significant complementation (indexes ~ 1). The ability of pairs of mutants to reassort at 39° generally followed a similar pattern. Thus interference is an important property of ts mutants of reovirus and needs to be considered when genetic interactions are being studied at 39°. 相似文献
36.
Ronald L. Arenson Dev P. Chakraborty Sridhar B. Seshadri Harold L. Kundel 《Journal of digital imaging》2003,16(1):142-162
Picture archiving and communication systems (PACS) are expected to convert film-based radiology into a computer-based digital environment, with associated cost savings and improved physician communication. The digital workstation will be used by physicians to display these soft-copy images; however, difficult technical challenges must be met for the workstation to compete successfully with the familiar viewbox. Issues relating to image perception and the impact on physicians practice must be carefully considered. The spatial and contrast resolutions required vary according to imaging modality, type of procedure, and class of user. Rule-based software allows simple physician interaction and speeds image display. A consensus appears to be emerging concerning the requirements for the PACS workstation. Standards such as the American College of Radiology/National Electrical Manufacturers Association Digital Imaging and Communication Standard are facilitating commercial applications. Yet much careful study is needed before PACS workstations will be fully integrated into radiology departments.
Abbreviations: CRT = cathode ray tube, H&D = Hurter and Drifield, PACS = picture archiving and communication system, ROC = receiver operating characteristic, S/N = signal-to-noise ratio. Partially supported by grant HL-33332 from the National Heart, Lung, and Blood institute, U.S. Public Health Service. Address reprint requests to R.L.A. Copyright © 1990 by the Radiological Society of North America. Radiology 176:303-315, 1990. Reprinted with permission. 相似文献
37.
Paola Paglia Ivano Arioli Nicole Frahm Trinad Chakraborty Mario P. Colombo Carlos A. Guzmn 《European journal of immunology》1997,27(6):1570-1575
Listeria monocytogenes has been proposed as a carrier to elicit major histocompatibility complex class-I restricted immune responses able to protect against tumor challenge. In this study the properties of the attenuated L. monocytogenes Δmpl2 mutant has been evaluated in vivo against a highly aggressive mouse fibrosarcoma which expresses β-galactosidase (β-gal) as a tumor-associated antigen (TAA). Immunization with the vaccine prototypes resulted in both elicitation of specific antibodies and generation of cytotoxic lymphocytes (CTL). Oral vaccination protected 55–64% of the immunized animals from tumor take (p < 0.01) and strongly reduced the average size of the tumor in the other 34–45% (p < 0.01). Vaccinated mice developed a long-lasting response, which resulted in 100% protection from a subsequent tumor challenge. Substitution of the whole TAA by its CTL-defined immunodominant epitope resulted in 43% protection, suggesting a contribution of the humoral response to the observed antitumor effect. No statistically significant differences were observed in the antitumor response when mice were immunized with strains expressing the immunodominant TAA epitope in the context of carrier proteins which were either exported or restricted to the bacterial cytoplasm. This suggests that the topology of the recombinant antigen does not play a major role in the outcome of the protective response. 相似文献
38.
Ranajit Chakraborty Ranjan Deka Li Jin Robert E. Ferrell 《American journal of human biology》1992,4(3):387-397
Because of their high degree of polymorphisms, the variable number of tandem repeat (VNTR) loci have become extremely useful in studies involving gene mapping, determination of identity and relatedness of individuals, and evolutionary relationships among populations. However, there are some concerns regarding whether or not the patterns of such genetic variation can be studied by the classical population models that are developed for studying genetic variation at blood groups and protein loci, since VNTR alleles detected by molecular size may not always be identical by descent. Although theoretical and empirical studies demonstrate that this concern is overstated, this study provides further support of the application of the traditional mutation-drift models to predict the pattern of intra- and inter-populational variation at VNTR loci. By comparing genetic variation at six VNTR loci with that at 16 blood groups and protein loci in three ethnically defined populations, we show that the patterns of variability at these two sets of loci are in general parallel to each other. Shared VNTR alleles among populations are generally more frequent than the ones which are not present in every population; the proportion of shared alleles among populations increases with increasing genetic similarity of populations; and the number of VNTR alleles is positively correlated with gene diversity at these loci. All of these observations are in agreement with the prediction of the mutation-drift models, particularly when the possibility of forward-backward mutations are taken into account. This parallelism of genetic variation at VNTR loci and blood groups/protein loci further asserts the potential of using such hypervariable loci for microevoltionary studies, where closely related populations may exhibit considerably less allele frequency differences at the classical blood group and protein loci. © 1992 Wiley-Liss, Inc. 相似文献
39.
Image intensifier distortion correction 总被引:2,自引:0,他引:2
D P Chakraborty 《Medical physics》1987,14(2):249-252
A method is described for determining and correcting the spatial distortion affecting images acquired with image-intensified video systems. The distortion is separated into two physically distinct components, a predominant one originating from the projection of the x-ray image onto the curved input phosphor, and a smaller component corresponding to the mapping from the input phosphor to the output phosphor and the digital image matrix. The former is determined geometrically and the latter is modeled with four empirical parameters. A method for determining the two components from calibration images of a grid phantom is presented. The model of the image intensifier distortion was found to be in good agreement with the measured distortion in the images. The correction is applicable to arbitrary angulations of the x-ray beam with respect to the image intensifier tube, and consequently is directly applicable to digital tomosynthesis. The correction allows one to obtain accurate positional information with fluorography and may also be useful in radiation therapy treatment planning and quantitative digital subtraction angiography. 相似文献
40.
Suppression of lymphokine-activated killer cell generation by tumor-infiltrating lymphocytes 总被引:1,自引:0,他引:1
N G Chakraborty J R Sporn D R Pasquale M T Ergin B Mukherji 《Clinical immunology and immunopathology》1991,59(3):407-416
A functional analysis of tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma (RCC) and malignant melanoma was performed. TILs were expanded in recombinant interleukin-2 (50 U/ml) in Iscoves medium. Phenotypic and functional (cytolytic vs regulatory) analyses were carried out with the fresh and expanded TIL populations after 4 weeks in culture. Only one TIL population from an RCC case (out of six cases studied) was CD8+ and demonstrated MHC class I-restricted tumor-specific cytotoxicity against the autologous RCC target. TIL populations from the other five cases became predominantly CD4+ and they neither killed the respective autologous tumor cells nor killed the NK-sensitive target K-562 cells. When studied for other functions, two CD4+ TIL populations were found to suppress the lymphokine-activated killer cell response by peripheral blood lymphocytes (PBL) in coculture. Of these two, a TIL population from an RCC case (MJ TIL) was used to study the cellular and molecular mechanisms of suppression. The MJ TIL synthesized a supernatant factor that blocked activation of resting PBL as measured by the induction of high-affinity IL-2 receptor (IL-2R) when stimulated by phytohemagglutinin but did not down-regulate the fully expressed IL-2R on activated T cells. The suppression of high-affinity IL-2R induction on T cells did not result from tumor necrosis factor-alpha and beta or from transforming growth factor-beta as these cytokines were not detected in the cell-free supernatant from the MJ TIL culture. The supernatant factor also suppressed IL-2-mediated enhancement of cytotoxicity by natural killer (NK) cells without demonstrating direct toxic effect on the NK cells. Thus, when TIL are used for adoptive immunocytotherapy, it may be useful to fully characterize them functionally, in vitro. 相似文献