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1.
Data collected from 25 cases of fetal or newborn death associated with maternal cocaine use are reported. The average week of gestation at which fetal death occurred was week 30. Abruptio placentae was observed in 7 cases and placental infarct was found in 4 cases. The average fetal blood cocaine and benzoylecgonine levels were 0.26 and 1.73 micrograms/mL. The average maternal levels were 0.14 and 1.80 micrograms/mL, respectively. 相似文献
2.
3.
Anti-idiotypes in B-cell tumor therapy 总被引:3,自引:0,他引:3
R A Miller J Lowder T C Meeker S Brown R Levy 《NCI monographs : a publication of the National Cancer Institute》1987,(3):131-134
Thirteen patients with B-cell lymphomas were treated with mouse monoclonal anti-idiotype antibodies. All but 1 of the patients in this study had received extensive prior treatment with conventional therapy for lymphoma. The treatment protocol initially included an escalating dose schedule which was intended to help us evaluate toxicity and pharmacokinetics and, eventually, to achieve appreciable levels of free mouse antibody in the circulation. The last 4 patients received substantial initial doses. Tumor sampling was performed before and during therapy for evaluation of tissue penetration by antibody. Patients received antibodies of gamma 1, 2a, or 2b isotype. None of the patients had serum paraproteins by routine clinical testing, but 6 had an idiotype protein detectable by a sensitive immunoassay at levels greater than 1 microgram/ml, two of which were greater than 200 micrograms/ml. These levels were temporarily reduced by plasma-pheresis. However, the presence of serum idiotype increased the requirement for mouse antibody to achieve tumor penetration. Another obstacle to treatment was immune response to mouse Ig that occurred in 5 of the 13 patients. Once an immune response had begun, further infusions of antibody failed to reach the tumor or induce tumor regression and were associated with toxicity. Our initial patient remains in an unmaintained complete remission 50 months after receiving antibody. Six of 12 additional patients have had objective remissions which also were clinically significant. However, these remissions were not complete. This therapy shows promise as an alternative modality for the treatment of B-cell lymphoma. We will need further studies to determine the mechanisms of the antitumor effect and to improve the clinical results. 相似文献
4.
BACKGROUND: Chronic renal failure (CRF) is associated with an atherogenic
lipid profile and an increased risk of ischaemic cardiovascular disease.
The associated hyperlipidaemia is reportedly ameliorated by erythropoietin
(Epo) therapy. According to a recent report, rats studied 3 weeks after 5/6
nephrectomy and fed a high- protein diet exhibited increased activities of
hepatic HMG-CoA reductase (HMG-CoAR) and cholesterol 7 alpha-hydroxylase
(Ch-7 alpha- H), despite normal corresponding mRNA values. DESIGN AND
METHODS: This study was designed to examine the effects of naturally
progressing CRF of longer duration as well as those of Epo therapy on gene
expressions of the key factors involved in hepatic cholesterol metabolism,
i.e., LDL receptor (LDLR), HMG-CoAR, and Ch-7 alpha-H. Sprague-Dawley rats
were randomized to the CRF group (5/6 nephrectomy), Epo-treated CRF group
(given Epo 150 U/kg/twice weekly) and sham-operated, placebo- treated
normal controls. They were allowed free access to regular rat chow and
studied 6 weeks after surgery. Liver mRNAs and protein mass or activities
of the above factors were studied. RESULTS: Plasma cholesterol
concentration was significantly increased in the CRF group (P < 0.001)
and was modestly lowered (P < 0.05) by Epo therapy. However, microsomal
cholesterol concentration and LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA as well
as HMG-CoAR activity, and Ch-7 alpha-H and LDLR protein mass measurements
were virtually identical in the three groups. Thus, hepatic LDLR, HMG-CoAR,
and Ch-7 alpha-H mRNA and protein measurements in rats with CRF were
similar to those of the normal control group representing an inappropriate
response to the associated hypercholesterolemia. Epo therapy led to partial
amelioration of CRF- associated hypercholesterolaemia with no discernible
effect on hepatic tissue expression of the above factors.
相似文献
5.
Rick B. Meeker 《Journal of neuroimmune pharmacology》2007,2(2):154-170
Invasion of human immunodeficiency virus (HIV) into the central and peripheral nervous system produces a wide range of neurological
symptoms, which continue to persist even with adequate therapeutic suppression of the systemic viremia. The development of
therapies designed to prevent the neurological complications of HIV require a detailed understanding of the mechanisms of
virus penetration into the nervous system, infection, and subsequent neuropathogenesis. These processes, however, are difficult
to study in humans. The identification of animal lentiviruses similar to HIV has provided useful models of HIV infection that
have greatly facilitated these efforts. This review summarizes contributions made from in vitro and in vivo studies on the infectious and pathological interactions of feline immunodeficiency virus (FIV) with the nervous system. In vivo studies on FIV have provided insights into the natural progression of CNS disease as well as the contribution of various
risk factors. In vitro studies have contributed to our understanding of immune cell trafficking, CNS infection and neuropathogenesis. Together,
these studies have made unique contributions to our understanding of (1) lentiviral interactions at the blood–cerebrospinal
fluid (CSF) barrier within the choroid plexus, (2) early FIV invasion and pathogenesis in the brain, and (3) lentiviral effects
on intracellular calcium deregulation and neuronal dysfunction. The ability to combine in vitro and in vivo studies on FIV offers enormous potential to explore neuropathogenic mechanisms and generate information necessary for the
development of effective therapeutic interventions. 相似文献
6.
7.
Serodiagnosis of leprosy: relationships between antibodies to Mycobacterium leprae phenolic glycolipid I and protein antigens. 总被引:9,自引:0,他引:9 下载免费PDF全文
W R Levis H C Meeker G B Schuller-Levis T P Gillis L J Marino Jr J Zabriskie 《Journal of clinical microbiology》1986,24(6):917-921
Sera from leprosy patients and controls were assayed for immunoglobulin M (IgM) and IgG antibodies to the Mycobacterium leprae-specific phenolic glycolipid I antigen (PG) by enzyme-linked immunosorbent assay, for IgG antibodies to M. leprae protein antigens by Western immunoblot, and for antibodies to a 65-kilodalton (kDa) protein antigen of M. leprae by a competition antibody binding assay. Elevated levels of anti-PG IgM were seen in lepromatous and borderline lepromatous patients, and elevated levels of anti-PG IgG were seen in borderline lepromatous patients. There was a significant correlation between the bacillary index (BI) and anti-PG IgM whether all leprosy patients or only multibacillary patients were analyzed. A significant correlation was seen between anti-PG IgG and BI when all leprosy patients were used for analysis, but not when only multibacillary patients were used. IgG antibodies to protein antigens of M. leprae, as detected by Western immunoblot, were more prevalent in lepromatous and borderline lepromatous patients than in borderline tuberculoid patients, while one of eight controls showed one weak band. There were significant correlations between the number of M. leprae protein antigens detected by the sera of patients and both BI and the level of anti-PG IgM. The 65-kDa competition antibody binding assay detected active multibacillary leprosy. Patients positive for antibody to the 65-kDa antigen had a significantly higher BI and levels of anti-PG IgM and anti-PG IgG than did patients that were negative. In addition, the level of antibody to the 65-kDa antigen correlated with both the BI and anti-PG IgM. We conclude that testing for antibodies to protein antigens of M. leprae may provide a useful adjunct to testing for antibodies to PG. 相似文献
8.
Prostate Stem Cell Compartments : Expression of the Cell Cycle Inhibitor p27Kip1 in Normal, Hyperplastic, and Neoplastic Cells 总被引:6,自引:4,他引:6 下载免费PDF全文
Angelo M. De Marzo Alan K. Meeker Jonathan I. Epstein Donald S. Coffey 《The American journal of pathology》1998,153(3):911-919
The stem cells of rapidly renewing tissues give rise to transiently proliferating cells, which in turn give rise to postmitotic terminally differentiated cells. Although the existence of a transiently proliferating compartment has been proposed for the prostate, little molecular anatomical evidence for its presence has been obtained to date. We used down-regulation of the cyclin-dependent kinase inhibitor p27Kip1 to identify cells capable of entering the proliferative phase of the cell cycle and, therefore, competent to fulfill the role of the transiently proliferating compartment. We examined the expression of p27Kip1 in relation to its role in the development of prostatic carcinoma. Formalin-fixed paraffin-embedded specimens from matched samples of normal-appearing prostate tissue, benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia, primary adenocarcinomas, and pelvic lymph node metastases were evaluated by comparative immunohistochemistry against p27Kip1. In normal-appearing prostate epithelium, moderate to strong nuclear staining of p27Kip1 was present in greater than 85% of the terminally differentiated secretory cells. The normal basal cell compartment, believed to contain prostatic stem cells, showed distinctive p27Kip1 expression; acini in epithelial benign prostatic hyperplasia tissue contained more p27Kip1-negative basal cells than acini from non-benign prostatic hyperplasia tissue. A third layer of cells was identified that was sandwiched between the basal cells and the luminal cells, and this layer was consistently p27Kip1 negative. This intermediate layer was accentuated in the periurethral region, as well as in prostate tissue that had been subjected to prior combined androgen blockade. We hypothesize that, on appropriate additional mitogenic stimulation, cells in this layer, and other p27Kip1-negative basal cells, are competent for rapid entry into the cell cycle. Consistent with the fact that cancer cells are capable of cell division, all cases of high-grade prostatic intraepithelial neoplasia and invasive carcinoma also showed down-regulation of p27Kip1 as compared with the surrounding normal-appearing secretory cells. In pelvic lymph node metastases, p27Kip1 expression was also reduced. In summary, our results suggest that lack of nuclear p27Kip1 protein may delineate a potential transiently proliferating subcompartment within the basal cell compartment of the human prostate. In addition, these studies support the hypothesis that reduced expression of p27Kip1 removes a block to the cell cycle in human prostate epithelial cells and that dysregulation of p27Kip1 protein levels may be a critical early event in the development of prostatic neoplasia. 相似文献
9.
Telomere lengths of translocation-associated and nontranslocation-associated sarcomas differ dramatically 下载免费PDF全文
Montgomery E Argani P Hicks JL DeMarzo AM Meeker AK 《The American journal of pathology》2004,164(5):1523-1529
Sarcomas can be divided into those with specific translocations displaying monotonous cytomorphology, and those with complex karyotypes and marked cellular pleomorphism. Telomeres contain terminal DNA sequence repeats that maintain chromosomal stability. Telomeres shorten with cell division and may become dysfunctional leading to chromosomal instability. Using a fluorescence in situ hybridization/immunofluorescence method to assess telomere lengths in archival tissues we analyzed these two types of sarcomas using paraffin-embedded primary tumor specimens. Tissues from nine sarcomas with characteristic translocations (two synovial sarcomas, two alveolar rhabdomyosarcomas, two desmoplastic round cell tumors, and one each of infantile fibrosarcoma, myxoid liposarcoma, cellular congenital mesoblastic nephroma) and nine without (four malignant fibrous histiocytomas, two leiomyosarcomas, one pleomorphic rhabdomyosarcoma, one dedifferentiated chondrosarcoma, and one malignant peripheral nerve sheath tumor) were analyzed. In all (nine of nine) cases with specific translocations, which generally have few karyotypic abnormalities, telomere lengths were similar to or reduced compared to surrounding nonneoplastic tissues. In contrast, telomeres in cases lacking specific translocations, which generally contain complex karyotypes, were often found to be dramatically lengthened and heterogeneous. In addition to markedly elongated telomeres, seven of nine (78%) complex cases exhibited large brightly stained regions corresponding to a specific type of promyelocytic leukemia nuclear body found in immortalized cells that maintain telomeres in a telomerase-independent manner [alternative lengthening of telomeres (ALT) pathway]. This phenotype is unlike that of epithelial neoplasms that typically display complex karyotypes with abnormally short telomeres maintained by the enzyme telomerase. The discovery of heterogeneous telomere lengths and evidence of the ALT pathway in the majority of sarcomas with complex karyotypes supports the existence of a telomere maintenance pathway incapable of full karyotypic stabilization in pleomorphic sarcomas. These findings provide additional molecular-genetic evidence supporting the dichotomous grouping of sarcomas into those with characteristic signature translocations without extensive additional karyotypic abnormalities, and those without such signature translocations that typically display very complex karyotypes, and point to telomere dysfunction as a plausible contributor to the chromosomal aberrations found in complex sarcomas. 相似文献
10.
Diana Cardenas MD PhD Gustavo Díaz RD MSc Jessika Cadavid ND MSC Fernando Lipovestky MD Marisa Canicoba RD Paola Sánchez MD Ludwig Álvarez ND Yan Duarte MD José Guillermo Gutiérrez Reyes MD Gilda Miranda de Noyola RD Claudia Maza RD Sergio Santana Porbén MD Charles Elleri Bermúdez MD Yawelida García RN Isabel Calvo RD Humberto Arenas MD 《JPEN. Journal of parenteral and enteral nutrition》2022,46(1):229-237