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971.
Protein C deficiency resulting from possible double heterozygosity and its response to danazol 总被引:1,自引:0,他引:1
A unique family with protein C (PC) deficiency is described. The proband had a history of renal vein thrombosis as a newborn and iliofemoral thrombosis at the age of 6 years. After 6 months of heparin treatment, discontinuation of anticoagulation therapy was accompanied by persistent hypofibrinogenemia with increased fibrinogen consumption. With continuous infusion of heparin, fibrinogen turnover normalized, and the child has remained free of thrombosis. Both the immunologic level of PC and the functional activity measured by amidolytic assay were moderately reduced (47% and 34%, respectively). Functional activity of PC measured by its anticoagulant activity was disproportionately lower (14%). A 3-year-old asymptomatic sibling had a similar disproportionate reduction of PC anticoagulant activity compared with the amidolytic activity or immunologic level. The mother demonstrated type I PC deficiency with a proportionate reduction in immunologic protein levels (59%), anticoagulant activity (52%), and amidolytic activity (46%), whereas the father had type II PC deficiency with normal immunologic protein levels (102%), normal amidolytic function (98%), but a low anticoagulant function (50%). An abnormal PC molecule was detected by two-dimensional immunoelectrophoresis in the father and two children. These data are consistent with the hypothesis that the children are doubly heterozygous for two different types of PC deficiency inherited from each of the parents. A 14-day trial of danazol in the proband resulted in a rise in the PC antigen concentration from 66% to 98% but no change in PC anticoagulant function. 相似文献
972.
Analysis of human platelet glycoproteins IIb-IIIa and Glanzmann's thrombasthenia in whole blood by flow cytometry 总被引:4,自引:0,他引:4
Antibodies that bind to human platelet membrane glycoproteins IIb and IIIa were used to develop methods for analyzing platelet membrane components by flow cytometry. Platelets were tentatively identified by their low-intensity light scatter profiles in whole blood or platelet- rich plasma preparations. Identification of this cell population as platelets was verified by using platelet-specific antibodies and fluorescein-conjugated antiimmunoglobulin. Two-parameter analysis of light scatter versus fluorescence intensity identified greater than 98% of the cells in the "platelet" light scatter profile as platelets due to their acquired fluorescence. Both platelet-rich plasma and whole blood were used to study platelet membrane glycoproteins IIb and IIIa on a single cell basis in an unwashed system. Prostacycline was included in these preparations as a precautionary step to inhibit platelet aggregation during analysis. Flow cytometry is a successful technique for rapid detection of platelet membrane defects such as Glanzmann's thrombasthenia. Platelets from Glanzmann's thrombasthenic individuals were readily distinguished from platelets with normal levels of glycoprotein IIb and IIIa and from platelets with glycoprotein levels characteristic of heterozygote carriers of this disorder. This technique provides a sensitive tool for investigating platelet functional defects due to altered expression or deficiency of platelet surface proteins. 相似文献
973.
Splenectomized mice treated for 7 days with pegylated recombinant rat stem cell factor (rrSCF-PEG) showed a dose-dependent increase in peripheral blood progenitor cells (PBPC) that have enhanced in vivo repopulating potential. A dose of rrSCF-PEG at 25 micrograms/kg/d for 7 days produced no significant increase in PBPC. However, when this dose of rrSCF-PEG was combined with an optimal dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 200 micrograms/kg/d), a synergistic increase in PBPC was observed. Compared with treatment with rhG-CSF alone, the combination of rrSCF-PEG plus rhG-CSF resulted in a synergistic increase in peripheral white blood cells, in the incidence and absolute numbers of PBPC, and in the incidence and absolute numbers of circulating cells with in vivo repopulating potential. These data suggest that low doses of SCF, which would have minimal, if any, effects in vivo, can synergize with optimal doses of rhG-CSF to enhance the mobilization of PBPC stimulated by rhG-CSF alone. 相似文献
974.
Kersten MJ; Evers LM; Dellemijn PL; van den Berg H; Portegies P; Hintzen RQ; van Lier RA; von dem Borne AE; van Oers RH 《Blood》1996,87(5):1985-1989
Diagnosis of meningeal localization of lymphoid malignancies by means of cytologic examination of the cerebrospinal fluid (CSF) can be difficult. Thus far no reliable CSF tumor markers have been identified. CD27 is a transmembrane disulfide-linked 55-kD homodimer present on most peripheral blood T cells and on a subset of B cells. CD27 is also expressed on human malignant B cells and high levels of soluble CD27 can be present in the serum of patients with B-cell malignancies. The aim of this study is to determine prospectively the diagnostic value of CSF sCD27 as a tumor marker in patients with meningeal localization of lymphoid malignancies. CSF sCD27 levels were determined by sandwich enzyme-linked immunosorbent assay. The optimal cut-off value using receiver operator characteristics curves was found to be 10 U/mL. sCD27 levels were normal in all 50 control patients (lumbar disc protrusion) and in 39 of 40 samples obtained from patients with either solid tumors or acute myeloid leukemia. Of 104 CSF samples from 70 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) undergoing routine central nervous system (CNS) staging, sCD27 was false positive and false negative in only one sample each. In 70 samples from 45 patients suspected of meningeal localization of ALL or NHL, the sCD27 test had an excellent sensitivity (100%) and specificity (82%). In 7 patients with positive CSF studied longitudinally, sCD27 levels correlated very well with remission and relapse. sCD27 levels were not nonspecifically increased by the administration of cytostatic drugs. Finally, sCD27 was also elevated in the 4 patients studied with primary central nervous system lymphoma (PCNSL). CSF sCD27 is a promising tumor marker in patients with either meningeal localization of lymphoid malignancies or PCNSL, and can be useful in the differential diagnosis of CNS involvement by either lymphoid malignancies or solid tumors. 相似文献
975.
Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases 总被引:8,自引:2,他引:8
Loss of a whole chromosome 7 or a deletion of the long arm, del(7q), are recurring abnormalities in malignant myeloid diseases. To determine the location of genes on 7q that are likely to play a role in leukemogenesis, we examined the deleted chromosome 7 homologs in a series of 81 patients with therapy-related or de novo myelodysplastic syndrome or acute myeloid leukemia. Our analysis showed that the deletions were interstitial and that there were two distinct deleted segments of 7q. The majority of patients (65 of 81 [80%]) had proximal breakpoints in bands q11-22 and distal breakpoints in q31-36; the smallest overlapping deleted segment was within q22. The remaining 16 patients had deletions involving the distal q arm with a commonly deleted segment of q32-33. To define the proximal deleted segment at 7q22 at a molecular level, we used fluorescence in situ hybridization with a panel of mapped yeast artificial chromosome (YAC) clones from 7q to examine 15 patients with deletion breakpoints in 7q22. We determined that the smallest overlapping deleted segment is contained in a well- defined YAC contig that spans 2 to 3 Mb. These studies delineate the region of 7q that must be searched to isolate a putative myeloid leukemia suppressor gene, and provide the necessary cloned DNA for more detailed physical mapping and gene isolation. 相似文献
976.
Collagen-induced arthritis in rhesus monkeys: evaluation of markers for inflammation and joint degradation 总被引:1,自引:0,他引:1
't Hart BA; Bank RA; De Roos JA; Brok H; Jonker M; Theuns HM; Hakimi J; Te Koppele JM 《Rheumatology (Oxford, England)》1998,37(3):314-323
The objective of this study was to analyse parameters in rhesus monkey
collagen-induced arthritis (CIA) with which the inflammation and
destruction of the joints can be described in quantitative terms. CIA was
induced in genetically susceptible and resistant monkeys, which can be
distinguished on the basis of the dominant resistance marker Mamu- A26. The
disease course was monitored daily using a semiquantitative scoring system.
Plasma samples were collected once or twice weekly and analysed for
C-reactive protein (CRP). Urines were collected overnight once a week and
analysed for excretion rates of the collagen cross- links
hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). The results show
that periods of active CIA are characterized by substantial weight loss and
increased plasma CRP levels, followed shortly thereafter by increased
excretion rates of the collagen cross- links HP and LP. Remission of the
disease can be recognized by a decline in plasma CRP levels and especially
an increase in body weight. The highest CRP levels were found in the most
severely arthritic monkeys, indicating a possible relationship of the
absolute plasma CRP levels to the severity of inflammation. During periods
of active arthritis, increased excretion rates of collagen cross-links HP
and LP in the urine were found. In particular, the major collagen
cross-link in articular cartilage, HP, showed a strong increase (9- to
15-fold). The excretion rates of LP, which is considered as a bone-specific
degradation marker, only increased 4- to 6-fold, thus indicating
predominant destruction of cartilage and less of bone. In conclusion, the
severity of CIA can be monitored in a quantitative manner using plasma CRP
levels, urinary excretion rates of HP and LP, and body weights,
superimposed on semiquantitative clinical scores. The parameters also
facilitate a more objective assessment of the effect of anti-arthritic
drugs in the model than with the clinical scores alone.
相似文献
977.
Alpha 4 beta 1-integrin expression on sickle reticulocytes: vascular cell adhesion molecule-1-dependent binding to endothelium 总被引:7,自引:4,他引:7
Important complications in sickle cell anemia occur secondary to vascular occlusion, which is postulated to be initiated by interactions of erythrocytes with vascular endothelial cells. In patients with sickle cell anemia, up to 25% of reticulocytes express the alpha 4 beta 1-integrin complex. Furthermore, erythrocytes from patients with sickle cell anemia bind to endothelial cells activated by tumor necrosis factor alpha via (TNF alpha) via interactions between erythrocyte alpha 4 beta 1 and endothelial cell vascular cell adhesion molecule-1 (VCAM- 1). Thus, binding of alpha 4 beta 1-expressing reticulocytes to cytokine-activated endothelial cells may initiate vascular complications in sickle cell anemia and perhaps other hemolytic anemias during episodes of infection and inflammation. 相似文献
978.
To determine whether cytomegalovirus (CMV) antigenemiaguided ganciclovir treatment may be as effective, may require less treatment, and thus may cause less marrow toxicity than ganciclovir administered at engraftment, 226 marrow transplant recipients were randomized at engraftment to receive placebo (antigenemia-ganciclovir group) or ganciclovir (ganciclovir group) until day 100 in a double-blind study. In patients with antigenemia of 3 or more positive cells in 2 slides and/or viremia, study drug was discontinued and ganciclovir was started for at least 3 weeks or until negative CMV antigenemia and resumed only if antigenemia recurred. More patients in the antigenemia-ganciclovir group developed CMV disease before day 100 after transplantation compared with the ganciclovir group (14% v 2.7%, P = .002). Of the 16 patients with CMV disease before day 100 in the antigenemia-ganciclovir group, 10 (8.8%) had disease before or during the first episode of antigenemia and 6 (5.3%) developed disease after discontinuation of ganciclovir. Untreated low-grade antigenemia progressed to CMV disease in 19% of patients with grade 3-4 compared with 0% of patients with grade 0-2 acute graft-versus-host disease (P = .04). There was no significant difference in CMV disease by day 180 after transplantation and thereafter. CMV-related death, transplant survival, and neutropenia were not significantly different between the groups. In the ganciclovir group, more invasive fungal infections occurred (P = .03) and more ganciclovir was used (P < .0001). Thus, delaying the start of ganciclovir until highgrade antigenemia and discontinuing ganciclovir based on negative antigenemia results in more CMV disease by day 100 than ganciclovir administered at engraftment. However, ganciclovir at engraftment is associated with more early invasive fungal infections and more late CMV disease resulting in similar survival rates. 相似文献
979.
Wildi SM Hoda RS Fickling W Schmulewitz N Varadarajulu S Roberts SS Ferguson B Hoffman BJ Hawes RH Wallace MB 《Gastrointestinal endoscopy》2003,58(3):362-368
BACKGROUND: Benign mediastinal cysts, which account for approximately 20% of mediastinal masses, may be diagnostic challenges. Information regarding the use of EUS and EUS-guided FNA in this setting is limited. The aim of this study was to demonstrate the value and potential risks of EUS and EUS-FNA in the diagnosis of mediastinal foregut cysts. METHODS: The EUS database of a single tertiary referral center was reviewed for the diagnosis of benign mediastinal cysts. Twenty patients were identified who underwent 23 EUS examinations for suspected mediastinal cysts (n = 4), for follow-up of a known cyst (n = 3), or for a mediastinal mass of unknown origin (n = 16). RESULTS: In 19 patients, the definite diagnosis of a mediastinal cyst was established by EUS. Twelve cysts appeared anechoic, 6 were hypoechoic, and one anechoic cyst contained small echoic foci. CT (n = 17) or magnetic resonance imaging (n = 1) was performed in 18 cases; only 4 of these were diagnostic of a cyst. In 3 cases, the cyst contents were aspirated by EUS-FNA. In a fourth case, a solid-appearing duplication cyst, misdiagnosed by EUS, was sampled with FNA and core biopsy. This patient developed severe sepsis secondary to mediastinitis 4 days later. Thoracotomy revealed an infected bronchogenic cyst. CONCLUSIONS: EUS provides a minimally invasive approach to the diagnosis of benign mediastinal cysts and may be more accurate than CT or other imaging modalities. Aspiration of suspected cysts should be undertaken with caution, given the risk of infection. 相似文献
980.