全文获取类型
收费全文 | 130篇 |
免费 | 6篇 |
国内免费 | 6篇 |
专业分类
儿科学 | 14篇 |
妇产科学 | 1篇 |
基础医学 | 18篇 |
口腔科学 | 8篇 |
临床医学 | 11篇 |
内科学 | 31篇 |
皮肤病学 | 3篇 |
神经病学 | 4篇 |
特种医学 | 38篇 |
外科学 | 2篇 |
综合类 | 1篇 |
预防医学 | 3篇 |
药学 | 3篇 |
肿瘤学 | 5篇 |
出版年
2019年 | 2篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 5篇 |
2013年 | 2篇 |
2012年 | 3篇 |
2011年 | 4篇 |
2010年 | 3篇 |
2009年 | 5篇 |
2008年 | 5篇 |
2007年 | 8篇 |
2006年 | 2篇 |
2005年 | 1篇 |
2004年 | 2篇 |
2003年 | 3篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 10篇 |
1997年 | 11篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1973年 | 2篇 |
排序方式: 共有142条查询结果,搜索用时 15 毫秒
1.
Gene conversion is a likely cause of mutation in PKD1 总被引:3,自引:0,他引:3
Watnick TJ; Gandolph MA; Weber H; Neumann HP; Germino GG 《Human molecular genetics》1998,7(8):1239-1243
Approximately 70% of the gene responsible for the most common form of
autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in
several highly homologous copies located more proximally on chromosome 16.
We recently have described a novel technique for mutation detection in the
duplicated region of PKD1 that circumvents the difficulties posed by these
homologs. We have used this method to identify two patients with a nearly
identical cluster of base pair substitutions in exon 23. Since pseudogenes
are known to be reservoirs for mutation via gene conversion events for a
number of other diseases, we decided to test whether these sequence
differences in PKD1 could have arisen as a result of this mechanism. Using
changes in restriction digest patterns, we were able to show that these
sequence substitutions are also present in N23HA, a rodent-human somatic
cell hybrid that contains only the PKD1 homologs. Moreover, these changes
were also detected in total DNA from several affected and unaffected
individuals that did not harbor this mutation in their PKD1 gene copy. This
is the first example of gene conversion in PKD1 , and our findings
highlight the importance of using gene-specific reagents in defining PKD1
mutations.
相似文献
2.
3.
BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis. (Gastroenterology 1996 Dec;111(6):1593-602) 相似文献
4.
Proton radiography and tomography have long promised benefit for proton therapy. Their first suggestion was in the early 1960s and the first published proton radiographs and CT images appeared in the late 1960s and 1970s, respectively. More than just providing anatomical images, proton transmission imaging provides the potential for the more accurate estimation of stopping-power ratio inside a patient and hence improved treatment planning and verification. With the recent explosion in growth of clinical proton therapy facilities, the time is perhaps ripe for the imaging modality to come to the fore. Yet many technical challenges remain to be solved before proton CT scanners become commonplace in the clinic. Research and development in this field is currently more active than at any time with several prototype designs emerging. This review introduces the principles of proton radiography and tomography, their historical developments, the raft of modern prototype systems and the primary design issues.Despite a history going back over 50 years,1 proton radiography (pRG) and tomography have been slow to reach the clinic.2 Few manufacturers currently offer a clinical imaging system suitable for pRG and none for proton tomography. In fact, it turns out that the use of protons instead of X-rays for transmission imaging has some disadvantages. These include the need for large expensive equipment to produce proton beams (e.g. a cyclotron or synchrotron) and the limitations on image quality arising from the multiple scattering of protons.Proton sources of sufficient energy do, however, exist for several purposes, one application being for proton therapy. The multiple scattering effects remain a fundamental difficulty: protons do not move through a medium in straight lines. So why should we even attempt proton transmission imaging? The prime motivation is with application to proton therapy planning. It was Cormack1 who was the first to realize the possibilities of proton CT (pCT). In a seminal article of the 1960s on tomographic reconstruction, the Nobel Laureate wrote:
Open in a separate windowaQuoted figure based on the scenario of 1-mm voxels and 180 projections, a target of 100 protons passing through a voxel per projection6 and a 10-min acquisition.bQuoted figure based on a crude calculation of comparable stochastic risk to typical X-ray CT head scans (≈40 mGy7,8), assuming a proton radiation weighting factor twice that of photons.9We will not be concerned here with other forms of imaging using proton beams, such as nuclear scattering tomography12 that relies on wide-angle scattering, γ interaction vertex imaging13 (GIVI) using prompt γ emission or positron emission tomography14 (PET) of induced β emission. The latter two (GIVI and PET) primarily promise benefit for in vivo range verification (inferring the depths that protons penetrated).15 Finally, we emphasize that our interest in this review is with protons. Reference to heavy-ion radiography and tomography will be made only where comparison with imaging with protons is apt, and we refer the reader to other sources16 for this related topic. 相似文献
The next application of the solution [for CT] … concerns the recent use of the peak in the Bragg curve for the ionization caused by protons, to produce small regions of high ionization in tissue. The radiotherapist is confronted with the problem of determining the energy of the incident protons necessary to produce the high ionization at just the right place, and this requires knowing the variable-specific ionization of the tissue through which the protons must pass.This is still a fair assessment of the problem facing any proton therapy team today. Cormack went on to propose that the energy loss of protons passing through a patient can tell us about proton stopping power inside the patient—something that X-rays can never give us directly.Typically, in both photon and proton external beam therapy, prior to treatment, an X-ray CT scan is acquired for treatment planning purposes. This is used for outlining structures, but also provides a map of electron density that is used to calculate dose deposition. In proton therapy, the translation of electron density to proton stopping power provides an extra and appreciable source of error. The most advanced X-ray CT calibration method in common usage is probably the stoichiometric method.3 The resulting overall uncertainty (1σ) in stopping-power ratio (SPR) for protons in different tissue types has been estimated as 1.6% (soft tissue), 2.4% (bone) and 5.0% (lung).4 As an illustration, note that the estimate of 1.6% for soft tissue includes contributions for (added in quadrature): stoichiometric parameterization (0.8%), human tissue composition variation (1.2%) and mean excitation energy (0.2%) and other sources (0.6%). None of the first three sources of errors contribute in a calibration in pCT and the ambition with this type of imaging should be to reduce the uncertainty in SPR substantially (to <1%). Reduced uncertainties offer the possibility of smaller planning margins and additional beam directions, potentially leading to superior patient outcomes. The surge in the number of operational and planned proton therapy centres in recent years therefore makes the exploitation of this modality timely.5Before proceeding further, some clarification of topic coverage should be made. pRG and pCT, in the context of this review, mean the imaging of an object using the transmission of protons through it. The energy loss of the transmitted protons is the primary mechanism for image contrast. The greatest emphasis will be given to proton-tracking systems: as will be seen, these are best able to cope with the difficulties imposed by proton multiple scattering. Some requirements for a practical pCT scanner for proton therapy are summarized in 10 For comparison, note that a typical head scan using a diagnostic X-ray CT scanner or X-ray cone beam CT (CBCT) might deliver 40 mGy.11
Table 1.
Requirements for a practical (proton-tracking) CT scanner for proton therapyCategory | Parameter | Value |
---|---|---|
Proton beam | Energy | ≥200 MeV (head) |
≥250 MeV (body) | ||
Fluxa | ≥3000 protons cm−2 s−2 | |
Imaging dose | Maximum absorbed doseb | <20 mGy |
Image quality | Spatial resolution, σ | ≈1 mm |
Relative stopping-power accuracy | <1% | |
Time | Data acquisition time | <10 min |
Reconstruction time | <10 min |
5.
Prostaglandin E2 (PGE2) is produced by activated platelets and by several other cells, including capillary endothelial cells. PGE2 exerts a dual effect on platelet aggregation: inhibitory, at high, supraphysiologic concentrations, and potentiating, at low concentrations. No information exists on the biochemical mechanisms through which PGE2 exerts its proaggregatory effect on human platelets. We have evaluated the activity of PGE2 on human platelets and have analyzed the second messenger pathways involved. PGE2 (5 to 500 nmol/L) significantly enhanced aggregation induced by subthreshold concentrations of U46619, thrombin, adenosine diphosphate (ADP), and phorbol 12-myristate 13-acetate (PMA) without simultaneously increasing calcium transients. At a high concentration (50 mumol/L), PGE2 inhibited both aggregation and calcium movements. PGE2 (5 to 500 nmol/L) significantly enhanced secretion of beta-thromboglobulin (beta TG) and adenosine triphosphate from U46619- and ADP-stimulated platelets, but it did not affect platelet shape change. PGE2 also increased the binding of radiolabeled fibrinogen to the platelet surface and increased the phosphorylation of the 47-kD protein in 32P- labeled platelets stimulated with subthreshold doses of U46619. Finally, the amplification of U46619-induced aggregation by PGE2 (500 nmol/L) was abolished by four different protein kinase C (PKC) inhibitors (calphostin C, staurosporine, H7, and TMB8). Our results suggest that PGE2 exerts its facilitating activity on agonist-induced platelet activation by priming PKC to activation by other agonists. PGE2 potentiates platelet activation at concentrations produced by activated platelets and may thus be of pathophysiologic relevance. 相似文献
6.
The penetration characteristics of electron beams into x-ray targets are investigated for incident electron kinetic energies in the range 50-150 keV. The frequency densities of electrons penetrating to a depth x in a target, with a fraction of initial kinetic energy, u, are calculated using Monte Carlo methods for beam energies of 50, 80, 100, 120 and 150 keV in a tungsten target. The frequency densities for 100 keV electrons in Al, Mo and Re targets are also calculated. A mixture of simple modeling with equations and interpolation from data is used to generalize the calculations in tungsten. Where possible, parameters derived from the Monte Carlo data are compared to experimental measurements. Previous electron transport approximations in the semiempirical models of other authors are discussed and related to this work. In particular, the crudity of the use of the Thomson-Whiddington law to describe electron penetration and energy loss is highlighted. The results presented here may be used towards calculating the target self-attenuation correction for bremsstrahlung photons emitted within a tungsten target. 相似文献
7.
Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia 总被引:7,自引:0,他引:7
The effects of recombinant interleukin-6 (IL-6) on the proliferation of blast precursors present in the peripheral blood of patients with acute myeloblastic leukemia (AML) was investigated. IL-6 had little effect by itself; however, it synergized with granulocyte macrophage colony- stimulating factor (GM-CSF) and interleukin-3 (IL-3) in the stimulation of AML blast colony formation. Responsiveness of blast progenitors to IL-6 was heterogeneous. On normal bone marrow cells the same synergy was observed on granulocyte and monocyte precursors (GM-CFC), while there was no significant effect on erythroid and multipotential precursors. 相似文献
8.
Background: The purpose of the present paper was to examine the attitudes and experiences of reporting child abuse and neglect among primary care and hospital‐based physicians and to study the responses of physicians and medical students to case vignettes suggestive of possible physical abuse or neglect. Methods: Physicians at the child health centers in Göteborg primary care (n= 44) and the general pediatricians at the pediatric hospital (n= 21) in Göteborg answered a questionnaire regarding their attitude and experiences reporting child abuse and neglect. The physicians and medical students (n= 34) responded to three case vignettes in which child abuse and neglect could be suspected. Results: A majority of the physicians had reported child abuse and neglect to the social services (80%). No differences were found between primary care and hospital‐based physicians in terms of reporting or attitudes. Two‐thirds of the physicians had suspected child abuse and neglect and decided not to report, and the major reason for not reporting was a lack of confidence in social services organization. Twenty‐one percent had never reported a child for abuse or neglect during their working career. Medical students were more likely to report hypothetical cases than physicians. Conclusion: Many physicians have reported child abuse to social services but also have neglected to do so even when suspecting abuse. It is important that medical students’ willingness to report is continued when starting to work clinically and that all physicians should be continuously educated. 相似文献
9.
Parathyroid adenomas evaluated by Tl-201/Tc-99m pertechnetate subtraction scintigraphy and high-resolution ultrasonography 总被引:2,自引:0,他引:2
Winzelberg GG; Hydovitz JD; O'Hara KR; Anderson KM; Turbiner E; Danowski TS; Lippe RD; Melada GA; Harrison AM 《Radiology》1985,155(1):231-235
Thallium-201/technetium-99m pertechnetate subtraction scintigraphy of the parathyroid glands was performed in a prospective study of 33 patients who had undergone bilateral neck exploration for elevated serum calcium and serum parathyroid hormone levels. In 31 cases, the Tl-201/Tc-99m subtraction technique yielded an overall sensitivity of 81%, specificity of 99%, and accuracy of 94% for identifying solitary parathyroid adenomas. Tl-201/Tc-99m subtraction scintigraphy correctly identified 73% of parathyroid adenomas weighing less than 499 mg, 79% of those weighing 500-1,499 mg, and 100% of adenomas weighing more than 1,500 mg. In a subgroup of 24 patients with solitary parathyroid adenomas who underwent both scintigraphy and high-resolution sonography, the sensitivity, specificity, and accuracy of both procedures were similar. 相似文献
10.
Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid cell-specific monoclonal antibodies 总被引:1,自引:0,他引:1
Second or third chemotherapy-induced remissions in acute myelogenous leukemia (AML) are limited by early relapse of the leukemia. We developed monoclonal antibodies (MoAbs) that are cytotoxic to myeloid leukemia cells to treat bone marrow from these patients ex vivo for autologous transplantation. In this pilot study, bone marrow was harvested from ten patients with AML in remission, treated with one or two complement-fixing MoAbs, PM-81 and AML-2-23, which react with myeloid differentiation antigens, incubated with rabbit complement, and cryopreserved. These MoAbs were chosen because they have broad reactivity with AML cells but not with pluripotent progenitor cells. At the time of transplant, 6 patients were in second complete remission, 1 each was in third complete or partial remission, and 2 were in early first relapse. The patients were treated with cyclophosphamide (60 mg/kg a day for 2 days) and total body irradiation (200 cGy twice a day for 3 days) and given infusions of MoAb-treated bone marrow. Full bone marrow reconstitution was observed in eight patients; two patients did not recover platelets. Seven of the ten patients are surviving and disease-free at 21.0, 15.0, 13.0, 10.0, 6.0, 3.0, and 2.0 months posttransplant. Treating bone marrow with MoAbs to myeloid differentiation antigens does not interfere with pluripotential stem cell engraftment. Longer follow-up and a controlled study are necessary to prove that the apparent efficacy of this therapeutic approach in some patients is attributable to MoAb-mediated killing of leukemia cells. 相似文献