全文获取类型
收费全文 | 907篇 |
免费 | 60篇 |
国内免费 | 17篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 31篇 |
妇产科学 | 4篇 |
基础医学 | 140篇 |
口腔科学 | 30篇 |
临床医学 | 92篇 |
内科学 | 230篇 |
皮肤病学 | 22篇 |
神经病学 | 67篇 |
特种医学 | 79篇 |
外科学 | 68篇 |
综合类 | 30篇 |
现状与发展 | 1篇 |
预防医学 | 32篇 |
眼科学 | 3篇 |
药学 | 71篇 |
中国医学 | 7篇 |
肿瘤学 | 74篇 |
出版年
2023年 | 5篇 |
2022年 | 6篇 |
2021年 | 21篇 |
2020年 | 12篇 |
2019年 | 11篇 |
2018年 | 11篇 |
2017年 | 13篇 |
2016年 | 20篇 |
2015年 | 27篇 |
2014年 | 32篇 |
2013年 | 39篇 |
2012年 | 67篇 |
2011年 | 50篇 |
2010年 | 56篇 |
2009年 | 39篇 |
2008年 | 55篇 |
2007年 | 50篇 |
2006年 | 41篇 |
2005年 | 44篇 |
2004年 | 42篇 |
2003年 | 26篇 |
2002年 | 26篇 |
2001年 | 24篇 |
2000年 | 24篇 |
1999年 | 17篇 |
1998年 | 29篇 |
1997年 | 18篇 |
1996年 | 21篇 |
1995年 | 8篇 |
1994年 | 14篇 |
1993年 | 9篇 |
1992年 | 4篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 12篇 |
1988年 | 14篇 |
1987年 | 19篇 |
1986年 | 12篇 |
1985年 | 7篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 8篇 |
1981年 | 2篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1976年 | 7篇 |
1975年 | 2篇 |
1971年 | 2篇 |
1967年 | 1篇 |
排序方式: 共有984条查询结果,搜索用时 15 毫秒
1.
Su Jeong Seong Jin Pyo Hong Bong-Jin Hahm Hong Jin Jeon Jee Hoon Sohn Jun Young Lee Maeng Je Cho 《Journal of Korean medical science》2015,30(11):1675-1681
While decreasing trend in gender differences in alcohol use disorders was reported in Western countries, the change in Asian countries is unknown. This study aims to explore the shifts in gender difference in alcohol abuse (AA) and dependence (AD) in Korea. We compared the data from two nation-wide community surveys to evaluate gender differences in lifetime AA and AD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Face-to-face interviews using the Composite International Diagnostic Interview (CIDI) were applied to all subjects in 2001 (n=6,220) and 2011 (n=6,022). Male-to-female ratio of odds was decreased from 6.41 (95% CI, 4.81-8.54) to 4.37 (95% CI, 3.35-5.71) for AA and from 3.75 (95% CI, 2.96-4.75) to 2.40 (95% CI, 1.80-3.19) for AD. Among those aged 18-29, gender gap even became statistically insignificant for AA (OR, 1.59; 95% CI, 0.97-2.63) and AD (OR, 1.18; 95% CI, 0.80-2.41) in 2011. Men generally showed decreased odds for AD (0.55; 95% CI, 0.45-0.67) and women aged 30-39 showed increased odds for AA (2.13; 95% CI 1.18-3.84) in 2011 compared to 2001. Decreased AD in men and increased AA in women seem to contribute to the decrease of gender gap. Increased risk for AA in young women suggests needs for interventions. 相似文献
2.
3.
Mary ER O'Brien Janet Hardy Sylvia Tan Jackie Walling Brian Peters Sarah Hatty Eve Wiltshaw 《Cancer chemotherapy and pharmacology》1992,30(3):245-248
Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted. 相似文献
4.
Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group 总被引:5,自引:0,他引:5
Haines JL; Terwedow HA; Burgess K; Pericak-Vance MA; Rimmler JB; Martin ER; Oksenberg JR; Lincoln R; Zhang DY; Banatao DR; Gatto N; Goodkin DE; Hauser SL 《Human molecular genetics》1998,7(8):1229-1234
Multiple sclerosis (MS) is a demyelinating autoimmune disease of the
central nervous system. While its etiology is not well understood, genetic
factors are clearly involved. Until recently, most genetic studies in MS
have been association studies using the case-control design testing
specific candidate genes and studying only sporadic cases. The only
consistently replicated finding has been an association with the HLA-DR2
allele within the major histocompatibility complex (MHC) on chromosome 6.
Using the genetic linkage design, however, evidence for and against linkage
of the MHC to MS has been found, fostering suggestions that sporadic and
familial MS have different etiologies. Most recently, two of four genomic
screens demonstrated linkage to the MHC, although specific allelic
associations were not tested. Here, a dataset of 98 multiplex families was
studied to test for an association to the HLA-DR2 allele in familial MS and
to determine if genetic linkage to the MHC was due solely to such an
association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta)
in the MHC demonstrated strong genetic linkage (parametric lod scores of
4.60, 2.20 and 1.24, respectively) and a specific association with the
HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results
by HLA-DR2 status showed that the linkage results were limited to families
segregating HLA-DR2 alleles. These results demonstrate that genetic linkage
to the MHC can be explained by the HLA-DR2 allelic association. They also
indicate that sporadic and familial MS share a common genetic
susceptibility. In addition, preliminary calculations suggest that the MHC
explains between 17 and 62% of the genetic etiology of MS. This
heterogeneity is also supported by the minority of families showing no
linkage or association with loci within the MHC.
相似文献
5.
P J Barr J Inselburg K M Green J Kansopon B K Hahm H L Gibson C T Lee-Ng D J Bzik W B Li I C Bathurst 《Molecular and biochemical parasitology》1991,45(1):159-170
We have expressed defined regions of the serine-repeat antigen (SERA) of the Honduras-1 strain of Plasmodium falciparum in the yeast Saccharomyces cerevisiae. Amino-terminal domains of the natural SERA protein have been shown previously to be targets for parasite-inhibitory murine monoclonal antibodies. Two recombinant SERA antigens were selected for purification and immunological analysis. The first (SERA 1), corresponding to amino acids 24-285 of the natural SERA precursor, was expressed by the ubiquitin fusion method. This allowed for in vivo cleavage by endogenous yeast ubiquitin hydrolase, and subsequent isolation of the mature polypeptide. The second, larger protein (SERA N), encompassing amino acids 24-506, was expressed at only low levels using this system, but could be isolated in high yields when fused to human gamma-interferon (gamma-IFN). Each purified protein was used to immunize mice with either Freund's adjuvant or a muramyl tripeptide adjuvant that has been used in humans. Sera from immunized mice were shown to be capable of in vitro inhibition of invasion of erythrocytes by the Honduras-1 strain of P. falciparum. The results suggest that a recombinant SERA antigen may be an effective component of a candidate malaria vaccine. 相似文献
6.
7.
Protective immunity induced in Aotus monkeys by recombinant SERA proteins of Plasmodium falciparum. 总被引:3,自引:9,他引:3 下载免费PDF全文
J Inselburg D J Bzik W B Li K M Green J Kansopon B K Hahm I C Bathurst P J Barr R N Rossan 《Infection and immunity》1991,59(4):1247-1250
We describe the vaccination of Panamanian monkeys (Aotus sp.) with two recombinant blood stage antigens that each contain a portion of the N-terminal region of the SERA (serine repeat antigen) protein of the malaria parasite Plasmodium falciparum. We immunized with either a 262-amino-acid SERA fragment (SERA I) that contains amino acids 24 to 285 of the 989-amino-acid protein or a 483-amino-acid SERA fragment (SERA N) that contains amino acids 24 to 506 as part of a fusion protein with human gamma interferon. The recombinant proteins were shown to stimulate protective immunity when administered with complete and incomplete Freund adjuvant. Four of six immunized monkeys challenged by intravenous inoculation with blood stage P. falciparum developed parasitemias that were reduced by at least 1,000-fold. Two of six immunized monkeys developed parasitemias which were comparable to the lowest parasitemia in one of four controls and were 50- to 1,000-fold lower than in the other three controls. 相似文献
8.
Contrast enhancement during the dynamic MR imaging is important for the detection and characterization of focal liver lesions. The purpose of this study was to determine whether or not a timing examination with a injection of a 1.0-mL bolus of gadopentetate dimeglumine into the antecubital vein followed by rapid dynamic scanning and measurement of signal intensity of the aorta could help to obtain proper arterial-dominant phase images for the characterization of focal hepatic lesions during subsequent multiphase dynamic MR imaging. The imaging delay to acquisition of the first gadolinium-enhanced image for multiphase dynamic MR imaging was set to equal the time to peak aortic enhancement during the test examination. The first contrast-enhanced images of 80 patients with 160 focal liver lesions (hepatocellular carcinoma, n = 79; cavernous hemangioma, n = 51; metastatic tumor, n = 30) were then retrospectively reviewed. Peak aortic enhancement occurred between 10 and 28 seconds (mean, 16.5 seconds +/- 3.1) after starting the infusion of contrast material in 80 patients during the test-examination. Depending on the findings of intrahepatic vascular enhancement on the full-scale dynamic images, hepatic arterial phase (n = 11, 14%) or sinusoid phase (n = 65, 81%) imaging was obtained during the first gadolinium-enhanced acquisition in 76 (95%) of 80 patients. Three different lesions were well characterized and easily distinguished from each other (p < .0001) on the first-phase images depending on their enhancement pattern. In the majority of patients, timing examination with test-bolus injection was helpful in obtaining qualified images for the characterization of various focal lesions. 相似文献
9.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
10.
Kim D Hur DY Kim YS Lee K Lee Y Cho D Kang JS Kim YI Hahm E Yang Y Yoon S Kim S Lee WB Park HY Kim YB Hwang YI Chang KY Lee WJ 《Human immunology》2002,63(7):576-587
Burkitt lymphoma (BL) is a tumor with the characteristics of germinal center B cells. We previously reported that the CM1 (centrocyte/-blast marker 1) molecule is expressed only in germinal center B cells, specifically, in a subpopulation of centroblasts and centrocytes. In the present study, we investigated the apoptosis induced by anti-CM1 in the Ramos and Raji human BL cell lines. The Ramos is protected from apoptosis by the crosslinking of sIgM and the calcium ionophore by the ligation of CD40 with anti-CD40 monoclonal antibodies (mAb) or soluble CD40 ligand (sCD40L). In this investigation on the effect of CM1 on apoptosis in BL cell lines, we found that cellular signaling by CM1 induces apoptosis and decreases cell viability, in BL cell lines cultured for 24 hours with protein-G agarose beads conjugated anti-CM1 mAb. Stimulation by CD40 ligated with sCD40L protected Raji cells from CM1-induced apoptosis, but did not protect Ramos cells. Furthermore, after anti-CM1 mAb stimulation, CD95 expression was upregulated and CD40 expression was unaltered or slightly decreased in Ramos cells, whereas CD95 was downregulated and CD40 was slightly upregulated in Raji cells. The engagement of CD40 by sCD40L enhanced CD95 expression, but the level of CM1 expression was unchanged in Ramos. However, sCD40L downregulated both CD95 and CM1 expression in Raji. In addition, the caspase-8 specific inhibitor blocked CM1-induced apoptosis in Ramos cells, but not in Raji cells. Increased mitochondrial membrane permeabilization was observed only in Raji cells. Moreover, the effector caspase inhibitor, z-DEVD, blocked CM1-mediated apoptosis in both cell lines. We found that CM1-induced apoptosis is achieved via different initiation pathways, which are cell-type dependent. 相似文献