全文获取类型
收费全文 | 429篇 |
免费 | 29篇 |
国内免费 | 13篇 |
专业分类
儿科学 | 22篇 |
妇产科学 | 2篇 |
基础医学 | 19篇 |
口腔科学 | 14篇 |
临床医学 | 55篇 |
内科学 | 77篇 |
皮肤病学 | 4篇 |
神经病学 | 6篇 |
特种医学 | 178篇 |
外科学 | 11篇 |
综合类 | 40篇 |
预防医学 | 6篇 |
眼科学 | 4篇 |
药学 | 9篇 |
1篇 | |
肿瘤学 | 23篇 |
出版年
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 5篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 5篇 |
2013年 | 2篇 |
2012年 | 9篇 |
2011年 | 9篇 |
2010年 | 8篇 |
2009年 | 10篇 |
2008年 | 1篇 |
2007年 | 13篇 |
2006年 | 11篇 |
2005年 | 10篇 |
2004年 | 5篇 |
2003年 | 10篇 |
2002年 | 3篇 |
2001年 | 6篇 |
2000年 | 1篇 |
1999年 | 5篇 |
1998年 | 24篇 |
1997年 | 23篇 |
1996年 | 17篇 |
1995年 | 23篇 |
1994年 | 20篇 |
1993年 | 33篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 9篇 |
1989年 | 17篇 |
1988年 | 21篇 |
1987年 | 34篇 |
1986年 | 21篇 |
1985年 | 20篇 |
1984年 | 8篇 |
1983年 | 12篇 |
1982年 | 6篇 |
1981年 | 12篇 |
1980年 | 12篇 |
1979年 | 1篇 |
1978年 | 7篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1971年 | 1篇 |
排序方式: 共有471条查询结果,搜索用时 15 毫秒
451.
452.
A pilot study of the human chorionic gonadotrophin test for ovarian hyperandrogenism 总被引:1,自引:4,他引:1
A controlled clinical study was designed to investigate the value of human
chorionic gonadotrophin (HCG) challenge as a test for functional ovarian
hyperandrogenism. Dexamethasone administration was followed by 5000 IU HCG
and blood samples for steroid hormone assay were obtained 0, 8, 16, and 24
h thereafter. Study subjects were normal women (n = 13); women with
functional ovarian hyperandrogenism, defined by androgen excess,
amenorrhoea and an increased 17-hydroxyprogesterone response to nafarelin
(n = 6); and normal men (n = 4). The responses of 17-hydroxyprogesterone,
androstenedione and testosterone to HCG in women with functional ovarian
hyperandrogenism were significantly greater than in normal women. However,
the 17-hydroxyprogesterone response to HCG in functional ovarian
hyperandrogenism was significantly lower after HCG than after nafarelin.
The oestradiol response was also significantly lower after HCG than
nafarelin, although oestradiol concentration more than doubled in normal
women as well as in women with functional ovarian hyperandrogenism. The
responses to HCG confirm that functional ovarian hyperandrogenism
abnormalities are luteinizing hormone (LH)-dependent. Therefore, the 17-
hydroxyprogesterone response to HCG could represent a useful test for the
diagnosis of ovarian hyperandrogenism. The lower 17- hydroxyprogesterone
response to HCG than to nafarelin in functional ovarian hyperandrogenism
suggests that a follicle-stimulating hormone (FSH)-responsive factor
modulates thecal 17-hydroxyprogesterone secretion. The oestradiol response
to HCG is consistent with HCG directly stimulating the oestradiol secretion
by thecal cells.
相似文献
453.
The 185delAG BRCA1 mutation originated before the dispersion of Jews in the diaspora and is not limited to Ashkenazim 总被引:4,自引:0,他引:4
Bar-Sade RB; Kruglikova A; Modan B; Gak E; Hirsh-Yechezkel G; Theodor L; Novikov I; Gershoni-Baruch R; Risel S; Papa MZ; Ben-Baruch G; Friedman E 《Human molecular genetics》1998,7(5):801-805
The 185delAG mutation in BRCA1 is detected in Ashkenazi Jews both in
familial breast and ovarian cancer and in the general population. All
tested Ashkenazi mutation carriers share the same allelic pattern at the
BRCA1 locus. Our previous study showed that this 'Ashkenazi' mutation also
occurs in Iraqi Jews with a similar allelic pattern. We extended our
analysis to other non-Ashkenazi subsets: 354 of Moroccan origin, 200
Yemenites and 150 Iranian Jews. Heteroduplex analysis complemented by
direct DNA sequencing of abnormally migrating bands were employed. Four of
Moroccan origin (1. 1%) and none of the Yemenites or Iranians was a carrier
of the 185delAG mutation. BRCA1 allelic patterns were determined for four
of these individuals and for 12 additional non-Ashkenazi 185delAG mutation
carriers who had breast/ovarian cancer. Six non-Ashkenazi individuals
shared the common 'Ashkenazi haplotype', four had a closely related
pattern, and the rest ( n = 6) displayed a distinct BRCA1 allelic pattern.
We conclude that the 185delAG BRCA1 mutation occurs in some non-Ashkenazi
populations at rates comparable with that of Ashkenazim. The majority of
Jewish 185delAG mutation carriers have a common allelic pattern, supporting
the founder effect notion, but dating the mutation's origin to an earlier
date than currently estimated. However, the different allelic pattern at
the BRCA1 locus even in some Jewish mutation carriers, might suggest that
the mutation arose independently.
相似文献
454.
Permissive recognition of immunodominant determinants of the retinal S- antigen in different rat strains, primates and humans 总被引:1,自引:0,他引:1
Fukushima A; Lai JC; Chanaud NP rd; Shiloach J; Whitcup SM; Nussenblatt RB; Gery I 《International immunology》1997,9(1):169-177
The majority of antigenic peptides exhibit restriction in their interaction
with the MHC molecules on antigen-presenting cells of different haplotypes.
Certain peptides, however, are "permissive': they bind strongly to
different MHC molecules and are selected as the immunodominant epitopes by
animals using these MHC gene products. Here we show for the first time that
several peptides from four regions of the sequence of human S-antigen
(H-SAg), a retinal-specific protein, demonstrate high levels of
permissiveness. Each of these peptides was found to be immunodominant in at
least some of four inbred rat strains and five cynomolgus monkeys,
immunized with whole H-SAg. Moreover, some of these peptides were
recognized by lymphocytes from four normal controls and four patients with
uveitis who responded against the H-SAg molecule. On the other hand, the
permissive peptides stimulated marginal or no response in cultures of Lewis
rats injected with adjuvant alone, or rat and human cell lines specific to
other antigens, thus demonstrating that these peptides do not carry any
non-specific mitogenic activity. One peptide, 29, which was found
immunodominant in the monkeys, the uveitis patients and Lewis rats, is
highly immunopathogenic in this rat strain. No good correlation between
immunodominance and immunopathogenicity was found with other H-SAg
peptides. The finding of cross-species permissiveness among peptides of
H-SAg and similar observations with myelin proteins suggest that
permissiveness could be quite prevalent among peptides of immunopathogenic
antigens.
相似文献
455.
The integrin alpha IIb beta 3, a calcium-dependent heterodimer, plays a critical role in platelet aggregation. The alpha IIb subunit of the heterodimer contains four highly conserved putative calcium-binding domains in its extracellular portion. During studies of the molecular basis of Glanzmann thrombasthenia in a child of mixed Caucasian background whose platelets expressed little alpha IIb beta 3 on their surface, we found the patient heterozygous for a two amino acid deletion in the fourth alpha IIb calcium-binding domain. When this alpha IIb mutant was expressed in COS-1 cells, we found that the deletion did not interfere with the assembly of alpha IIb beta 3 heterodimers, but altered their conformation such that they were neither recognized by the heterodimer-specific antibody A2A9 nor able to undergo further intracellular processing or transport to the cell surface. These results suggest that the calcium-binding domains in alpha IIb play an important role maintaining the overall conformation of alpha IIb beta 3. To confirm this suggestion, we deleted each of the four 12 amino acid calcium-binding domains in alpha IIb by in vitro mutagenesis and expressed the mutants along with beta 3 in COS-1 cells. Each construct formed a heterodimer with beta 3, but none of the heterodimers interacted with A2A9 or underwent further intracellular processing. These data indicate that the calcium-binding domains in alpha IIb are not involved in alpha IIb beta 3 heterodimer formation, but their presence is required for the intracellular transport of alpha IIb beta 3 to the cell surface. 相似文献
456.
Canine model for gene therapy: inefficient gene expression in dogs reconstituted with autologous marrow infected with retroviral vectors 总被引:11,自引:2,他引:11
Successful retroviral gene transfer into murine hematopoietic stem cells indicates the potential for somatic gene therapy in the treatment of certain human hereditary diseases. We developed a canine model to test the applicability of these techniques to a preclinical model of human marrow transplantation. Previously we reported that canine CFU-GM could be infected with retroviral vectors carrying either the gene for a mutant dihydrofolate reductase (DHFR) or neomycin phosphotransferase (NEO). This study reports six lethally irradiated dogs transplanted with autologous marrow cocultivated with retroviral vector-producing cells. This procedure conferred drug resistance to 3% to 13% of the CFU- GM. Three dogs infected with either the NEO or DHFR virus engrafted, but we detected no drug-resistant CFU-GM. Three dogs were given marrow infected with a DHFR virus and received methotrexate (MTX) as in vivo selection; all three had evidence of engraftment. In the surviving dog, we detected 0.03% to 0.1% MTX-resistant CFU-GM at 3 to 5 weeks posttransplant during in vivo selection. These results indicate that we can reconstitute lethally irradiated dogs with autologous marrow exposed to retroviral vectors and suggest that gene transfer into hematopoietic cells is feasible on a large scale. However, the low- level transient gene expression indicates that considerable obstacles remain before human gene therapy can be considered. 相似文献
457.
Nanotechnology is the branch of science which deals with particles ranging between 1–100 nm. These particles are called nanoparticles, and they exhibit unique electronic, optical, magnetic, and mechanical properties, which make them different from the bulk material. These properties of nanomaterials help them to find a variety of applications in the biomedical, agricultural, and environmental domains. Cerium oxide nanoparticles have gained a lot of attention as a potential future candidate for ending various kinds of problems by exhibiting redox activity, free radical scavenging property, biofilm inhibition, etc. Synthesis of these nanoparticles can be performed very easily by utilizing chemical or biological methods. But in this review, the focus is laid on the biosynthesis of these nanoparticles; as the biosynthesis method makes the cerium oxide nanoparticle less toxic and compatible with the living tissues, which helps them to find their path as an anticancer, anti-inflammatory and antibacterial agents. The pre-existing reviews have only focused on details relating to properties/applications/synthesis; whereas this review draws attention towards all the aspects in single review covering all the details in depth such as biosynthesis methods and its effect on the living tissues, along with properties, biomedical applications (diagnostic and therapeutic) and future outlook of the cerium oxide nanoparticle.Cerium oxide nanoparticles have revolutionized the biomedical field and is still in very fast pace of development. Hence, this work elaborates the physicochemical properties, biosynthesis, and biomedical applications of cerium oxide nanoparticles. 相似文献
458.
Geller RB; Saral R; Piantadosi S; Zahurak M; Vogelsang GB; Wingard JR; Ambinder RF; Beschorner WB; Braine HG; Burns WH 《Blood》1989,73(8):2209-2218
Ninety-nine patients with acute nonlymphocytic leukemia (ANLL) received HLA-identical bone marrow transplants (BMTs) from sibling donors after preparation with high doses of busulfan and cyclophosphamide. Forty- nine patients were transplanted in first complete remission (CR), and 50 patients were transplanted in second and third CR and early relapse. Fifty-three received one of three regimens containing primarily low- dose cyclophosphamide (group I) for graft-v-host disease (GVHD) prophylaxis; since March 1983, 46 patients received intravenous (IV) cyclosporine (group II). After December 1983, only cytomegalovirus (CMV)-seronegative blood products were used in appropriate patients, and since April 1984 patients seropositive for herpes-simplex virus (HSV) and CMV received high-dose acyclovir prophylaxis. For patients transplanted in first CR, there was a significantly lower incidence of acute GVHD (P = .005) and deaths related to GVHD and interstitial pneumonitis (P = .001) in patients in group II. This was reflected in an improved Kaplan-Meier probability of disease-free survival (DFS) in the 22 patients transplanted in group II as compared with the 27 patients in group I (64% +/- 10% v 30% +/- 9%, P = .017). The probability of remaining in remission was slightly lower in group II (82% +/- 9% v 94% +/- 6%, P = .479). For patients transplanted in second and third CR and early relapse, the incidence of acute GVHD (P = .026) and deaths related to GVHD and interstitial pneumonitis was significantly lower in group II (P = .029); the probability of remaining in remission was also less (47% +/- 15% v 91% +/- 15%, P = .022). However, the probability of DFS was not significantly different between the two groups (26% +/- 10% v 35% +/- 18%, P = .957). We conclude that transplantation for patients in first CR who received IV cyclosporine therapy is effective treatment; patients with more refractory disease treated with the same cyclosporine regimen (group II) had a lower incidence of GVHD than those treated in group I, but survival did not improve because of an increase in the number of relapses and other nonleukemic complications. 相似文献
459.
Effects of lipid A and liposomes containing lipid A on platelet and fibrinogen production in rabbits 总被引:3,自引:0,他引:3
The effect of the lipid A moiety of endotoxin on platelet and fibrinogen production was studied in rabbits. Lipid A was infused intravenously in doses ranging from 1 to 100 micrograms/kg body mass; 18 hr later, selenomethionine-75Se was injected intravenously and its incorporation into fibrinogen and platelets determined. Lipid A in saline stimulated fibrinogen and platelet production, but the dose required was 50--100 times that required for an intact endotoxin. Although lipid A solubilized in triethylamine (TEA) was at least 60 times more active in the Limulus amebocyte lysate assay than was lipid A suspended in saline, the sensitivity of platelet and fibrinogen production to solubilized lipid A was increased only twofold. Incorporation of lipid A into liposomes had no effect on its Limulus activity. Lipid A in liposomes continued to stimulate platelet, but not fibrinogen, production. Leukopenia that was induced by lipid A in TEA did not occur when rabbits received the same dose of lipid A in liposomes. Lipid A, like intact endotoxin, can stimulate platelet and fibrinogen production and induce leukopenia but the doses required are high. The low solubility of lipid A in aqueous solutions may be only one factor that determines its biologic activity. 相似文献
460.
Holden JT; Geller RB; Farhi DC; Holland HK; Stempora LL; Phillips CN; Bray RA 《Blood》1995,86(1):60-65
Thy-1 (CDw90) is a phosphatidylinositol-anchored cell surface molecule which, when coexpressed with CD34 in normal human bone marrow, identifies a population of immature cells that includes putative hematopoietic stem cells. To date, the characterization of Thy-1 expression has been confined largely to normal tissues and cell lines. In this study, we evaluated the frequency and intensity of Thy-1 expression as defined by reactivity with the anti-Thy-1 antibody 5E10 in 38 cases of CD34+ acute leukemia (21 acute myelogenous leukemia [AML], 8 chronic myelogenous leukemia [CML] in blast crisis, and 9 acute lymphoblastic leukemia [ALL]). In 34 of 38 cases (89%) the CD34+ cells lacked expression of the Thy-1 antigen. High-density Thy-1 expression was found in 1 case of CML in lymphoid blast crisis, and low- density Thy-1 expression was identified on a portion of the leukemic cells in 2 cases of AML with myelodysplastic features, and 1 case of CML in myeloid blast crisis, suggesting a possible correlation between Thy-1 expression and certain instances of stem cell disorders such as CML and AML with dysplastic features. In contrast, the dissociation of Thy-1 and CD34 expression in the majority of acute leukemias studied suggests that the development of these leukemias occurs at a later stage than the hematopoietic stem cell. Characterization of Thy-1 expression in acute leukemia may eventually provide insights into the origin of the disease. In addition, separation of leukemic blasts from normal stem cells based on Thy-1 expression may prove useful in assessing residual disease, as well as in excluding leukemic blasts from stem cell preparations destined for autologous bone marrow or peripheral stem cell transplantation. 相似文献