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排序方式: 共有349条查询结果,搜索用时 15 毫秒
31.
32.
Expression of bcl-xL can confer a multidrug resistance phenotype 总被引:14,自引:3,他引:14
It has been suggested that genes that regulate apoptotic cell death may play an important role in determining the sensitivity of tumor cells to chemotherapy. We have recently cloned a member of the bcl-2 family, bcl- x. To test whether bcl-XL expression affects the sensitivity of tumor cells to chemotherapy, we have created stable cell lines overexpressing bcl-XL and have tested these cells for resistance to cell death induced by metabolic inhibitors and chemotherapeutic agents. Bcl-XL expression dramatically reduces the cytotoxicity of bleomycin, cisplatin, etoposide, vincristine, hygromycin B, and mycophenolic acid for up to 4 days in culture. Bcl-XL does not prevent cells from undergoing cell cycle arrest in response to these drugs, but rather prevents treated cells from undergoing apoptosis. Cell-cycle analysis on cells treated with the chemotherapeutic agents bleomycin, cisplatin, etoposide, and vincristine, show that the drugs cause growth arrest in different positions within the cell cycle. Bcl-XL expressing cells treated with chemotherapeutic drugs retain their proliferative ability after the drugs are removed. Interestingly, vincristine-treated cells expressing bcl-XL become polyploid after drug removal. These data show that bcl-XL protects cells from a wide variety of apoptotic stimuli, acts in multiple positions within the cell cycle, and confers a multidrug resistance phenotype. The ability of bcl-XL to prevent apoptotic cell death in response to chemotherapy-induced DNA damage and cell-cycle arrest may contribute to the accumulation of chromosomal aberrations within tumors. The expression of bcl-XL in tumor cells is likely to be an important indicator of chemotherapeutic efficacy. 相似文献
33.
LeLorier J Bombardier C Burgess E Moist L Wright N Cartier P Huckell V Hunt R Nawar T Tobe S 《The Canadian journal of cardiology》2002,18(12):1301-1308
BACKGROUND: Selective cyclo-oxygenase (COX)-2 inhibitors (coxibs) produce the beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) while sparing the COX-1-mediated adverse effects on platelets and the gastrointestinal system. However, due to the presence of constitutive COX-2 in the human kidney, coxibs have the same potential for adverse renal effects as traditional NSAIDs. OBJECTIVE: To provide evidence-based guidelines for the use of traditional NSAIDs and coxibs in patients potentially at risk for renal and associated hemodynamic blood pressure effects. METHODS: All pertinent peer-reviewed papers were retrieved with the usual electronic search tools. RESULTS: Both traditional NSAIDs and coxibs compromise the glomerular filtration rate in patients at increased risk. If there are differences in the blood pressure-raising potential of these drugs, these differences do not appear to be clinically significant. CONCLUSIONS: The blood pressure should be monitored for all patients taking chronic NSAID or coxib therapy. If a clinically significant (4 to 5 mmHg or more) increase in blood pressure is detected, the NSAID or the coxib should be discontinued and replaced with acetaminophen, to which codeine might be added. If the NSAID or the coxib is considered necessary, the increase in blood pressure should be treated. In addition, if the glomerular filtration rate reserve is compromised, all patients (including those taking short term therapy) should be closely monitored for the early detection of signs and symptoms of renal failure. 相似文献
34.
In vitro characterization of the human recombinant soluble granulocyte- macrophage colony-stimulating factor receptor 总被引:1,自引:0,他引:1
We have cloned, expressed, and partially purified a naturally occurring, truncated, soluble form of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit to investigate its biochemical and biologic properties. The soluble receptor species lacks the transmembrane and cytoplasmic domains that are presumably removed from the intact receptor cDNA by a mechanism of alternative splicing. The resulting soluble 55- to 60-kD glycosylated receptor species binds GM-CSF with a dissociation constant (kd) of 3.8 nmol/L. The soluble GM-CSF receptor successfully competes for GM-CSF binding not only with the transmembrane-anchored GM-CSF receptor alpha subunit but also with the native oligomeric high-affinity receptor complex. In addition, in human bone marrow colony-forming assays, the soluble GM-CSF receptor species can antagonize the activity of GM-CSF. Our data suggest that the soluble GM-CSF receptor may be capable of acting in vivo as a modulator of the biologic activity of GM-CSF. 相似文献
35.
36.
Trabecular bone architecture in female renal allograft recipients-- assessed by computed tomography 总被引:1,自引:0,他引:1
Grotz WH; Mundinger FA; Muller CB; Rasenack J; Schulte-Monting J; Langer MF; Schollmeyer PJ 《Nephrology, dialysis, transplantation》1997,12(3):564-569
BACKGROUND: Osteopenia with decreased bone mineral density (BMD) is a
frequent finding in renal allograft recipients. Data concerning the bone
architecture in these patients do not exist, however. METHODS: We compared
the bone architecture of 33 randomly assigned women (age 49 +/- 12 years),
who had received renal allografts 5.6 +/- 5.3 years before the
investigation, with 74 women (age 50 +/- 14 years) who were admitted for
osteodensitometry. All patients underwent single-energy computed tomography
(SEQCT) and a midvertebral high-resolution tomography with
computer-assisted analysis of the trabecular vertebral body architecture.
RESULTS: Progressive alteration of bone architecture was associated with
increasing vertebral height loss of the vertebral body. Height reduction of
a vertebral body of more than 15% was associated with a significantly lower
BMD (-2.3 +/- 0.8 versus -1.1 +/- 1.1 standard deviations below normal
BMD), a lower trabecular bone area (13 +/- 8% versus 42 +/- 22%) and a
lower trabecular diameter (1.4 +/- 0.5 mm versus 2.2 +/- 0.8 mm) compared
to recipients without height reduction. In comparison to a matched group of
patients with similarly reduced BMD (1.1 +/- 1.2 versus 1.2 +/- 1.1 SD
below normal BMD), renal allograft recipients showed a lower number of
trabecular plates (5.6 +/- 3.1 versus 7.0 +/- 3.7) and a smaller
intertrabecular surface (54 +/- 116 mm versus 75 +/- 138 mm). CONCLUSIONS:
Alterations of bone architecture in renal allograft recipients were
associated with progressive vertebral height loss. Despite similar bone
mineral density, differences of bone architecture could be observed between
renal allograft recipients and patients with osteoporosis.
相似文献
37.
Differentiation of thrombi from slow flow in the pulmonary arteries, sometimes observed in the presence of pulmonary arterial hypertension, can be equivocal. Magnetic resonance (MR) imaging was performed in a patient with chronic pulmonary thromboembolism and pulmonary arterial hypertension using an electrocardiographically gated technique that allowed visualization of the pulmonary arteries at the end of diastole and multiple times during systole. These images were compared with those of a patient with primary pulmonary hypertension and those of healthy subjects. Thrombi were discrete structures, seen throughout the cardiac cycle on both the first and second spin-echo images, and decreased in signal intensity on the second image. Slow flow increased in signal intensity and changed in structure during the cardiac cycle and was seen best on the second image. MR may play an important role in excluding large central thrombi as the cause of pulmonary arterial hypertension. It is a noninvasive method for defining pulmonary arterial wall thickness and for direct visualization of chronic pulmonary thrombus. 相似文献
38.
Six human hematopoetic cell lines were successfully heterotransplanted into athymic (nude) and asplenic-athymic (lasat) neonatal mice. The tumors arising from leukemia and lymphoma cells could then be serially transplanted into adult nude mice. Seven days after the fourth serial mouse passage, each mouse was treated with goat immune gamma globulin against K-562 cells. One control group was treated similarly, but with nonimmune (normal) gamma globulin, while another control group was not treated. The goat gamma globulin was not toxic for nude and lasat mice, and the immune, but not the normal, gamma globulin suppressed local subcutaneous growth of myelosarcomas, lymphosarcomas, and Burkitt lymphoma cells. On the other hand, the growth of lung, breast, and prostatic carcinomas and a melanoma of human origin were not altered by the immune gamma globulin. Since suppression of cell growth occurred equally well in decomplemented mice, a complement-mediated cytotoxicity apparently cannot be considered as responsible for the abrogation. The Fab fragment of the immunoglobulin did not suppress the growth of the myelosarcomas. We conclude that antibody suppression of the in vivo proliferation was specific for malignant hematopoietic cells and that the Fc portion of IgG is necessary for in vivo cytolysis of leukemia cells. The most probable mechanisms are direct antibody cytolysis and antibody-dependent macrophage-mediated cytotoxicity. 相似文献
39.
J G Webb C R Kerr V F Huckell H F Mizgala D R Ricci 《The American journal of cardiology》1986,58(6):568-570
40.
Yuanyuan Wu Kathryn CB Tan Sammy WM Shiu Yishan Luo Lin Shi Timothy CY Kwok 《Journal of diabetes investigation.》2022,13(11):1873
Aims/IntroductionTo examine the association between cholesterol efflux capacity (CEC) of serum high‐density lipoprotein (HDL) and cognitive function and brain structures in older people with diabetes mellitus.Materials and MethodsParticipants of a randomized placebo‐controlled trial of 27‐month vitamin B12 supplementation in older people with diabetes mellitus, which showed no effect on cognition, were further followed up at month 72. Cognitive tests included the Clinical Dementia Rating scale, Neuropsychological Test Battery in memory, executive function and psychomotor speed. Brain magnetic resonance imaging scans were carried out in a subset at baseline, month 27 and month 45. Fasting serum at baseline, month 9, month 27 and month 72 were analyzed for adenosine triphosphate‐binding cassette transporter A1‐mediated CEC of HDL and apolipoprotein A1 (ApoA1).ResultsSerum HDL cholesterol at baseline was associated with better executive and memory function at follow up. Serum ApoA1 was associated with a better memory Z‐score at month 18. Serum CEC and ApoA1 were not associated with Clinical Dementia Rating scale, Neuropsychological Test Battery, hippocampal volume and white matter disease on magnetic resonance imaging at baseline and whole brain atrophy rates. They were also not associated with cognitive function at month 27 and 72 on multilevel modeling. CEC and ApoA1 decreased significantly from baseline to month 27. Faster decliners in CEC had a greater increase in brain peak width of skeletonized mean diffusivity.ConclusionsHigher serum HDL cholesterol was associated with more favorable changes in memory and executive function in older people with diabetes mellitus. However, this was not due to CEC or ApoA1. A decline in CEC was associated with small vessel disease in the brain. 相似文献