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991.
Crist WM; Shuster JJ; Falletta J; Pullen DJ; Berard CW; Vietti TJ; Alvarado CS; Roper MA; Prasthofer E; Grossi CE 《Blood》1988,72(6):1891-1897
The immunophenotypes of lymphoblasts from children with newly diagnosed T-cell acute lymphoid leukemia (T-ALL, n = 101) or T-cell non-Hodgkin lymphoma (T-NHL, n = 31) were analyzed to correlate stage of thymocyte differentiation with clinical features and outcome. The 67 boys and 34 girls with T-ALL were 1 month to 18 years old (median, 8 years) with leukocyte counts ranging from 2 to 810 x 10(9)/L (median, 55 x 10(9)/L). Eighteen of these patients were black, and 70 had a mediastinal mass. Twenty-six boys and five girls with a median age of 9 years (range, 1 to 20 years) had T-NHL. Seven of these patients were black, and 24 had a mediastinal mass. The distributions of thymocyte developmental stages (early [CD7+], intermediate [CD1+ and/or CD4+ and/or CD8+], and mature [CD3+]) in cases of T-ALL and T-NHL were significantly different: 34%, 43%, and 23% v 6%, 62%, and 32% (P = .02). A comparison of the patients' clinical features according to the maturational stage of thymocytes failed to disclose significant differences in the majority of characteristics studied. However, patients with mature-stage T-NHL, with or without the addition of subjects with mature-stage T-ALL, were less likely to have a mediastinal mass (P = .02 for both comparisons). Those with intermediate-stage T-cell malignancy (T-ALL and T-NHL combined) were the subgroup most likely to have a mediastinal mass (P = .01). Response to remission induction therapy was significantly worse in the T-ALL subgroup with an early-stage phenotype: a failure rate of 21% v 0% and 6% for the two more differentiated phenotypic subgroups (P = .007). Event-free survival was not affected by thymocyte maturational stage in cases of either T-ALL or T-NHL. Despite evidence of clinical heterogeneity among the maturational stages of T-cell malignancies in children, these developmental subdivisions do not appear to be critical determinants of outcome once remission is achieved. We conclude that such phenotypes need not be included in the stratification plans for clinical trials using common induction treatment. 相似文献
992.
Goan SR; Fichtner I; Just U; Karawajew L; Schultze W; Krause KP; von Harsdorf S; von Schilling C; Herrmann F 《Blood》1995,86(1):89-100
Mononuclear cells (MNCs) containing peripheral blood stem cells (PBSCs) were obtained from solid-tumor patients undergoing mobilizing chemotherapy followed by granulocyte colony-stimulating factor for PBSC transplantation-supported dose-intensified anticancer chemotherapy and were transplanted into unconditioned "nonleaky" young severe combined immunodeficient mice. Multilineage engraftment was shown by flow cytometry and immunocytochemistry using monoclonal antibodies to various human cell surface antigens as well as identification of human immunoglobulin in murine sera. Within a dose range of MNCs suitable for transplantation (10 to 36 x 10(6) cells/graft) the number of CD34+ cells injected (optimal at > 0.7 x 10(6)/graft) determined the yield of human cells produced in recipient animals. Engraftment of hu PBSC preparations resulted in prolonged generation of physiologic levels of human cytokines including interleukin-3 (IL-3), IL-6, and granulocyte- macrophage colony-stimulating factor, which were detectable in the murine blood over a period of at least 4 months. In vivo survival of immature human progenitor cells was preserved even 9 months after transplantation. Because human IL-3 is known to stimulate early hematopoiesis, a rat fibroblast cell line was stably transfected with a retroviral vector carrying the human IL-3 gene and cotransplanted subcutaneously as additional source of growth factor. Cotransplants of this cell line producing sustained in vivo levels of circulating human IL-3 for at least 12 weeks significantly accelerated the process of engraftment of huPBSC and spurred the spread of mature human cells to the murine spleen, liver, thymus, and peripheral blood. Cotransplants of allogeneic human bone marrow stromal cells derived from long-term cultures resulted in a comparable--though less prominent--support of engraftment. 相似文献
993.
A cell-based screen for resistance of Bcr-Abl-positive leukemia identifies the mutation pattern for PD166326, an alternative Abl kinase inhibitor 总被引:2,自引:5,他引:2 下载免费PDF全文
von Bubnoff N Veach DR van der Kuip H Aulitzky WE Sänger J Seipel P Bornmann WG Peschel C Clarkson B Duyster J 《Blood》2005,105(4):1652-1659
In Philadelphia-positive (Ph(+)) leukemia, point mutations within the Bcr-Abl kinase domain emerged as a major mechanism of resistance to imatinib mesylate. We established a cell-based screening strategy for detection of clinically relevant point mutations using Bcr-Abl-transformed Ba/F3 cells. We identified 32 different single-point mutations within the kinase domain of Bcr-Abl. The pattern and frequency of mutations in this cell culture-based screen resembled the pattern and frequency observed in resistant patients. We then applied this screen to an alternative Abl kinase inhibitor. Using PD166326, the frequency of resistant colonies emerging at 5 to 10 times the median growth inhibition (IC50) of PD166326 was significantly lower than with imatinib. In addition, PD166326 produced a distinct pattern of Bcr-Abl mutations. The majority of mutations that came up with both imatinib and PD166326 could effectively be suppressed by increasing the dose of PD166326 to 50 to 500 nM. In contrast, only a few mutations could be suppressed by increasing the imatinib dose to 5 to 10 microM. However, 3 mutations affecting F317 displayed complete resistance to PD166326, but could be effectively inhibited by standard concentrations of imatinib. Thus, this robust and simple screening system provides a rational basis for combinatorial and sequential treatment strategies in targeted cancer therapy. 相似文献
994.
995.
OBJECTIVE: To study the predictive factors for avascular necrosis (AVN) of
bone in patients with systemic lupus erythematosus (SLE). METHOD: The
records of 38 SLE patients who developed clinically apparent AVN during the
course of their disease were reviewed. Information on clinical
presentation, corticosteroid usage and autoantibody profiles was obtained,
and comparison was made between these patients and 143 consecutive control
SLE patients who did not have AVN. RESULTS: The point prevalence of AVN in
our SLE population was 12%. Patients with AVN, when compared with controls,
had a significantly higher incidence of neurological disease (39% vs 14%; P
< 0.001) and Cushingoid body habitus after steroid treatment (79% vs
53%; P = 0.004). The highest cumulative prednisolone dose in 1 and 4 months
was significantly higher in the AVN group than the controls (1.8 vs 1.1 and
4.5 vs 2.8 g, respectively; P < 0.01 in both) and showed a linear trend
with the incidence of AVN (chi2 test for trend, P < 0.01 in both). Lupus
anticoagulant was associated with AVN (P = 0.02, odds ratio 2.88 [1.14-
7.28]). Logistic regression analysis revealed that the highest cumulative
prednisolone dose administered in 4 months, the maximum and mean daily
prednisolone dosage, and the lupus anticoagulant were independent risk
factors for AVN. CONCLUSIONS: Corticosteroid remains the major predisposing
factor for AVN in SLE. Patients who require an initial high-dose steroid
for disease control are at risk of AVN, especially if they are positive for
the lupus anticoagulant or develop Cushingoid habitus after steroid
treatment. High-risk patients should be closely monitored so that early AVN
can be diagnosed by sensitive techniques such as magnetic resonance imaging
and radioisotope bone scanning.
相似文献
996.
Dr. R. Zimmermann G. Ehlers W. Ehlers H. von Voss U. Göbel U. Wahn 《Annals of hematology》1979,38(2):119-125
Summary Four new cases with congenital homozygous factor VII deficiency are described. Factor VII levels were reduced to <1%,3%,8% and 10%, respectively. The incidence and severity of bleeding symptoms were well correlated with the measured factor VII activity. In the severe case of factor VII deficiency (<1%) a home treatment program was started because of severe recurrent hemarthroses. This entailed transfusions of 20 U/kg body weight prothrombin complex or factor VII concentrate in case of acute bleeding approximately every three weeks. These transfusions have been carried out successfully without any problems. In contradiction, two brothers with hypoproconvertinemia (factor VII 8% and 10%, respectively) reached an age of more than 70 years. Despite replacement therapy postoperative bleeding followed one appendectomy, whereas no postoperative bleeding followed patients requiring Achilles tendon lengthening and an above knee amputation and only slight bleeding followed a tonsillectomy. Based on our experience we suggest that in patients with factor VII deficiency of less than 10%, when undergoing surgery, should be maintained a minimal factor VII activity of 10–15% during the first three postoperative days. 相似文献
997.
Major histocompatibility complex-linked immune-responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice. 总被引:56,自引:11,他引:56 下载免费PDF全文
H von Boehmer W Haas N K Jerne 《Proceedings of the National Academy of Sciences of the United States of America》1978,75(5):2439-2442
Female murine T cells can respond to the Y antigen of male cells by generating cytotoxic T-killer lymphocytes. Responsiveness is linked to several H-2 genes. Two types of low responders can be distinguished: the B10.A(5R) (H-2i5) strain, a low responder because it lacks Y-specific precursor T cells able to differentiate into cytotoxic T-killer cells; and the CBA/J (H-2k) strain, a low responder because it lacks Y-specific T-helper cells able to support differentiation of T-killer cell precursors. B10.A(5R) stem cells differentiating in an x-irradiated (CBA/J X C57BL/6) (H-2k X H-2b)F1 host respond to Y antigen by generating T-killer cells whereas CBA/J stem cells do not. The results are consistent with the hypothesis that diversity of T-cell receptors is generated by somatic mutation of germ-line genes encoding specificity for self-H-2. A detailed account of this hypothesis is presented. 相似文献
998.
Evaluation of aortic coarctation after surgical repair: role of magnetic resonance imaging and Doppler ultrasound. 总被引:2,自引:0,他引:2 下载免费PDF全文
E G Mühler J M Neuerburg A Rüben R G Grabitz R W Günther B J Messmer G von Bernuth 《Heart (British Cardiac Society)》1993,70(3):285-290
OBJECTIVE--To compare the usefulness of magnetic resonance imaging (MRI) and Doppler ultrasound with that of cross sectional echocardiography and oscillometric blood pressure measurement for the evaluation of aortic coarctation after surgical repair. DESIGN--Prospective study. Aortic diameters measured by cross sectional echocardiography, MRI, and angiography (selected cases) and functional data determined by physical examination, oscillometric blood pressure measurement, and continuous wave Doppler. SETTING--Tertiary referral centre. PATIENTS--40 patients aged 2-28 years (mean 10.6 years) who had had surgical correction of aortic coarctation (mean follow up 5.7 years). RESULTS--In all patients MRI gave diameter measurements of the aortic arch and the thoracic aorta whereas in half of them cross sectional echocardiographic measurement of the isthmic region failed. The correlation coefficient for aortic diameters measured by MRI and angiography was 0.97 and that between MRI and echocardiography was 0.89. Peak velocities in the descending aorta correlated better with residual narrowing of the aortic isthmus or distal aortic arch or both than systolic blood pressure gradients between the upper and lower limbs. A peak velocity of < 2 m/s in the descending aorta during systole excluded important restenosis. Prolongation of anterograde blood flow during diastole always indicated a morphological abnormality--either important restenosis or aneurysmal dilatation. CONCLUSIONS--MRI was better than cross sectional echocardiography for imaging the aortic arch after coarctation repair and measuring its diameter. Peak velocity in the descending aorta correlated better with residual stenosis than did the systolic blood pressure gradient between the upper and lower limbs and this index could be used to indicate a need for MRI. 相似文献
999.
delta-Aminolevulinate dehydratase in human erythroleukemia cells: an immunologically distinct enzyme 总被引:4,自引:0,他引:4
Physicochemical and immunologic properties of delta-aminolevulinate (ALA) dehydratase in human K562 erythroleukemia cells were examined. ALA dehydratase activity was found to increase in K562 cells after treatment with butyric acid or selenium oxide. Enzyme activity in untreated K562 cells was comparable to that in normal adult erythrocytes but was increased three- to six-fold in K562 cells treated with 1.2 mmol/L butyric acid or 0.03 mmol/L selenium oxide. The Michaelis-Menten constant (Km), the inhibitor constant (Ki), and elution profile by diethylaminoethyl (DEAE) cellulose chromatography were similar for ALA dehydratase from K562 cells and normal human adult and human fetal erythrocytes. However, ALA dehydratase from K562 cells did not react with a monospecific rabbit antibody against ALA dehydratase purified from normal adult erythrocytes, although the antibody reacted with the enzyme from normal adult and fetal red cells. These findings indicate that ALA dehydratase in K562 cells is immunologically distinct from the normal enzyme. 相似文献
1000.
von Laer D Corovic A Vogt B Herwig U Roscher S Fehse B Baum C 《Bone marrow transplantation》2000,25(Z2):S75-S79
One restriction of retroviral gene transfer into hematopoietic stem cells is the low level of amphotropic virus receptor. In the present study, we examined whether retroviral vectors pseudotyped with the G-protein of vesicular stomatitis virus (VSV) can overcome this restriction. Human progenitor cells purified by magnetic beads and cell sorting were transduced with an amphotropic or VSV-G-pseudotyped retroviral vector containing the truncated human nerve growth factor receptor as a marker gene. Cells were prestimulated with flt-3 ligand, stem cell factor, and interleukin-3 and transduced on fibronectin. Marker gene expression was analyzed by flow cytometry. Transduction efficiencies of amphotropic and VSV-G-pseudotyped virus for CD34+ cells did not differ significantly. Gene transfer into CD34+CD38- cells, which are enriched in more immature progenitors, was not restricted and transfer efficiencies for this subset were also similar for both pseudotypes. The addition of fibronectin improved gene transfer with the amphotropic vector considerably (5- to 19.3-fold, mean 12.6), while the effect on the VSV-G-pseudotype was far less pronounced (1- to 3.9-fold, mean 2.1, P = 0.04). In conclusion, high levels of gene transfer to human hematopoietic progenitors were achieved with an optimized transduction protocol, and transduction efficiencies could not be improved further by the use of VSV-G-pseudotypes. 相似文献