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991.
992.
Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy 总被引:4,自引:6,他引:4
McNally EM; Duggan D; Gorospe JR; Bonnemann CG; Fanin M; Pegoraro E; Lidov HG; Noguchi S; Ozawa E; Finkel RS; Cruse RP; Angelini C; Kunkel LM; Hoffman EP 《Human molecular genetics》1996,5(11):1841-1847
Recently, mutations in the genes encoding several of the dystrophin-
associated proteins have been identified that produce phenotypes ranging
from severe Duchenne-like autosomal recessive muscular dystrophy to the
milder limb-girdle muscular dystrophies (LGMDs). LGMD type 2C is generally
associated with a more severe clinical course and is prevalent in northern
Africa. A previous study identified a single base pair deletion in the gene
encoding the dystrophin-associated protein gamma-sarcoglycan in a number of
Tunisian muscular dystrophy patients. To investigate whether
gamma-sarcoglycan gene mutations cause autosomal recessive muscular
dystrophy in other populations, we studied 50 muscular dystrophy patients
from the United States and Italy. The muscle biopsies from these 50
patients showed no abnormality of dystrophin but did show diminished
immunostaining for the dystrophin- associated protein alpha-sarcoglycan.
Four patients with a severe muscular dystrophy phenotype were identified
with homozygous, frameshifting mutations in gamma-sarcoglycan. Two of the
four have microdeletions that disrupt the distal carboxyl-terminus of
gamma- sarcoglycan yet result in a complete absence of gamma-and beta-
sarcoglycan suggesting the importance of this region for stability of the
sarcoglycan complex. This region of gamma-sarcoglycan, like beta-
sarcoglycan, has a number of cysteine residues similar to those in
epidermal growth factor cysteine-rich regions.
相似文献
993.
Anderson RA; Wallace EM; Groome NP; Bellis AJ; Wu FC 《Human reproduction (Oxford, England)》1997,12(4):746-751
Inhibin has been postulated to be secreted by Sertoli cells in response to
follicle stimulating hormone (FSH) and in turn to exert an inhibitory
effect on FSH production. We have investigated this relationship using an
assay specific for dimeric inhibin B. A total of 56 normal men received 200
mg testosterone enanthate (TE) i.m. weekly, for 65 +/- 1 weeks in a trial
of hormonal male contraception. Before treatment a significant negative
correlation between inhibin B and FSH concentration (r = 0.49, P <
0.001) was observed. During TE treatment, luteinizing hormone (LH) and FSH
were rapidly suppressed. This was followed by a parallel decline in inhibin
B and sperm concentration. During the early recovery phase, inhibin B
concentrations remained suppressed in men who showed a delay in resumption
of spermatogenesis, despite higher FSH concentrations. Inhibin B returned
to pretreatment concentrations after 24 weeks recovery, when the inverse
relationship with FSH was restored. Our results showed the expected inverse
physiological relationship between inhibin B and FSH in normal men, with a
decline during TE treatment and alpha subsequent resumption of the inverse
relationship during recovery. These data clearly support the hypothesis
that inhibin B plays a physiological role in the feedback control of FSH
secretion, and reflects FSH-stimulated Sertoli cell function.
相似文献
994.
Genetic analysis of tumerigenesis: XVI. Chromosome changes in azacytidine- and insulin-induced tumorigenesis 总被引:5,自引:0,他引:5
Chromosome changes accompanying differentiation and tumorigenesis in azacytidine- (azaC) and insulin-induced preadipocytes of the Chinese hamster embryo fibroblast cell line CHEF/18 are described. Karyotype analysis of 47 clones, subclones, and tumor-derived cells has shown that trisomy for chromosome 3q (mar 1) is characteristic of azaC preadipocytes but not of insulin preadipocytes. AzaC preadipocytes were consistently tumorigenic as well as trisomic for chromosome 3q, whereas most insulin preadipocytes were nontumorigenic and diploid. Only the few insulin preadipocytes that were tumorigenic were also trisomic for chromosome 3q. Among the tumor-derived cell lines recovered from azaC preadipocytes injected into nude mice, four had no additional chromosome changes except trisomy for 3q, as detected by karyotype analysis. Thus trisomy for 3q may be a sufficient chromosome change to induce tumor-forming ability in these cells. The rearrangements of chromosome 3 seen in this and other work pinpoint the trisomic region between the centromere and 3q5. 相似文献
995.
Co-ligation of alpha4beta1 integrin and TCR rescues human thymocytes from steroid-induced apoptosis 总被引:1,自引:0,他引:1
Zaitseva MB; Mojcik CF; Salomon DR; Shevach EM; Golding H 《International immunology》1998,10(10):1551-1561
Maturation of thymocytes represents a sequence of events during which
thymocytes expressing TCR with moderate avidity for self antigen/MHC are
positively selected, whereas those with high or insufficient TCR avidity
die. Glucocorticoids are produced intrathymically and can contribute to
apoptosis of unselected thymocytes. Thymocytes differentiate in a close
contact with epithelial cells, expressing vascular adhesion molecule-1
(VCAM-1) and secreting glucocorticoids, with bone marrow-derived
macrophages, and with extracellular matrix containing fibronectin (FN) and
collagen. Their contact with FN is mediated by alpha4beta1 and alpha5beta1
integrins. We examined the contribution of TCR and integrin signaling to
the survival of thymocytes from dexamethasone (Dex)-induced apoptosis. We
demonstrate that FN and VCAM-1 (both of which bind alpha4beta1 integrin),
but not collagen, considerably augment TCR-mediated protection of
thymocytes from Dex-induced apoptosis. This 'survival' signal is transduced
through the alphabeta1, but not through the alpha5beta1 integrin. The
observed protection from Dex-induced apoptosis correlated with an increase
in bcl-2 protein levels. FN-alpha4beta1 and VCAM-1-alpha4beta1 engagement
induced up-regulation bcl-2 protein, while alpha5beta1 binding to FN
induced a negative signal that was blocked by anti- alpha5beta1 antibody.
These data suggest that alpha4beta1 integrin may contribute to protection
of thymocytes with moderate avidity TCR from glucocorticoid-induced death
during intrathymic maturation.
相似文献
996.
PRL-3 expression in metastatic cancers. 总被引:27,自引:0,他引:27
Alberto Bardelli Saurabh Saha Jason A Sager Kathy E Romans Baozhong Xin Sanford D Markowitz Christoph Lengauer Victor E Velculescu Kenneth W Kinzler Bert Vogelstein 《Clinical cancer research》2003,9(15):5607-5615
PURPOSE: Expression of the PRL-3 tyrosine phosphatase is elevated in liver metastases derived from colorectal cancer (CRC). We sought to determine the cellular basis of this elevation and assess the expression of PRL-3 in metastatic lesions derived from cancers of the colon and other tissues. EXPERIMENTAL DESIGN: We developed modifications of in situ hybridization methods that facilitated the study of paraffin-embedded sections. We also evaluated PRL-3 gene copy numbers using fluorescence in situ hybridization and developed antibodies to assess PRL-3 subcellular localization. RESULTS: PRL-3 mRNA expression was elevated in nearly all metastatic lesions derived from CRCs, regardless of the site of metastasis (liver, lung, brain, or ovary). Expression was found in neoplastic cells, although tumor endothelium also expressed the gene. In contrast, little or no PRL-3 expression was observed in normal colon, nonmetastatic primary cancers, or metastatic lesions derived from cancers other than those of the colon (pancreas, stomach, or esophagus). Interphase fluorescence in situ hybridization confirmed that gene amplification was not the major cause of PRL-3 overexpression. Immunohistochemical analysis with anti-PRL-3 antibodies showed a cell membrane localization, consistent with the predicted isoprenylation of the protein. CONCLUSIONS: These studies establish an unexpected and unprecedented specificity in metastatic gene expression profiles: PRL-3 is apparently expressed in CRC metastases to any organ but is not expressed in metastases of other cancers to the same organs or in nonmetastatic CRCs. PRL-3 is also expressed in tumor vasculature, regardless of the tumor source. These data raise intriguing questions about the role of protein phosphorylation in angiogenesis and cell-type-specific metastatic processes. 相似文献
997.
Hayley A Hutchings Penney Upton Wai-Yee Cheung Alison Maddocks Christine Eiser John G Williams Ian T Russell Sonia Jackson Meriel EM Jenney 《Health and quality of life outcomes》2008,6(1):19
Background
Although it is now widely endorsed that children should as far as possible rate their own health related quality of life (HRQL), there are situations where proxy information on child HRQL may be useful, especially where a child is too ill or young to provide their own HRQL assessment. There is limited availability of generic HRQL scales that have a parallel child and parent version and that are reliable, valid, brief, comprehensible and suitable for use in UK populations. The aims of this study were therefore to develop and validate a parent version of the anglicised Manchester-Minneapolis Quality of Life child form (MMQL-UK (CF)) and to determine the level of association between the child and parent versions of this form. 相似文献998.
Skaane P Sager EM Olsen JB Abdelnoor M Berger A Wolff PA Kullmann G 《Acta radiologica (Stockholm, Sweden : 1987)》1999,40(2):163-168
PURPOSE: To analyze the diagnostic accuracy of mammography, ultrasonography (US), and both methods combined in evaluation of palpable noncalcified breast tumors. MATERIAL AND METHODS: Mammograms and sonograms of 200 patients with palpable noncalcified breast masses were retrospectively analyzed independently by four experienced radiologists in 3 sessions: Mammography or US interpretations in the first two and combined reading in the last session. Nonneoplastic abnormalities and mammographically obvious cancers were excluded. Receiver operating characteristic (ROC) analyses were performed for 115 (60 benign and 55 malignant) tumors and subgroups according to tissue density and tumor size. A single ROC curve for each diagnostic test was obtained by pooling the individual ratings. The area under the ROC curve was used as a measure of diagnostic performance. RESULTS: US revealed significantly higher diagnostic performance than mammography for tumors larger than 2 cm. Combined reading showed significantly higher performance than mammography except for tumors smaller than 2 cm. The performance of all three tests was reduced in dense parenchyma, and significantly so for mammographic and combined interpretation. CONCLUSION: The accuracy of US in patients with palpable mammographically noncalcified and not obviously malignant breast tumors is lower than reported for mixed sample populations. The accuracy of US may be influenced by breast parenchyma density. Combined reading offers the highest diagnostic accuracy. 相似文献
999.
Mahoney JE Sager MA Jalaluddin M 《The journals of gerontology. Series A, Biological sciences and medical sciences》1999,54(2):M83-M88
BACKGROUND: Loss of functional independence occurs frequently with hospitalization. In community-dwelling elders, lower extremity disability is an important predictor of functional loss. Ambulation assistive devices (canes, walkers), as markers of lower extremity disability, may predict functional decline associated with hospitalization, but this has not been evaluated previously. We sought to determine the association of mobility impairment, as indicated by cane or walker use prehospitalization, with adverse outcomes at hospital discharge and 3 months post discharge. METHODS: Subjects were community-dwelling adults (N = 1212) aged 70 and older, hospitalized for acute medical illness. The study was a secondary analysis of the Hospital Outcomes Project for the Elderly, a prospective randomized trial at three university and two private acute-care hospitals, which randomized patients to usual care or an intervention group designed to maintain functional abilities. RESULTS: After controlling for demographic and illness-related characteristics and prehospital function, mobility impairment was significantly associated with functional decline. Use of a walker was associated with 2.8 times increased risk for decline in ADL function by hospital discharge (p = .0002). Three months after discharge, patients who used assistive devices prior to hospitalization were more likely to have declined in both ADLs (p = .02) and IADLs (p = .003). CONCLUSIONS: Hospitalized patients with mobility impairment, as indicated by use of a cane or a walker, are at high risk for functional decline. Such patients may benefit from more intensive in-hospital and post-hospital rehabilitative therapy to maintain function. 相似文献
1000.
MD Shields EM Hicks DF Macgregor S Richey 《Acta paediatrica (Oslo, Norway : 1992)》1995,84(2):215-217
We report on a 6-month-old infant with asthma who developed spasms and hypsarrhythmia on the electroencephalogram (EEG) shortly after starting oral theophylline medication. Theophylline levels at that time were just above the upper normal range. The spasms stopped and the EEG normalized when theophylline was discontinued and nitrazepam therapy started. On follow-up over the next 3 years there was no recurrence of seizures and the chilďs neurodevelopment has been normal. Nitrazepam was stopped at 10 months and the waking and sleeping EEG were normal at 14 months. We believe that the infantile spasms were caused by theophylline. 相似文献