全文获取类型
收费全文 | 1049篇 |
免费 | 99篇 |
国内免费 | 46篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 76篇 |
妇产科学 | 31篇 |
基础医学 | 97篇 |
口腔科学 | 39篇 |
临床医学 | 170篇 |
内科学 | 221篇 |
皮肤病学 | 27篇 |
神经病学 | 56篇 |
特种医学 | 165篇 |
外科学 | 72篇 |
综合类 | 27篇 |
预防医学 | 65篇 |
眼科学 | 12篇 |
药学 | 60篇 |
1篇 | |
中国医学 | 9篇 |
肿瘤学 | 60篇 |
出版年
2023年 | 2篇 |
2021年 | 11篇 |
2020年 | 9篇 |
2019年 | 6篇 |
2018年 | 21篇 |
2017年 | 23篇 |
2016年 | 25篇 |
2015年 | 30篇 |
2014年 | 37篇 |
2013年 | 47篇 |
2012年 | 21篇 |
2011年 | 38篇 |
2010年 | 47篇 |
2009年 | 72篇 |
2008年 | 32篇 |
2007年 | 54篇 |
2006年 | 20篇 |
2005年 | 25篇 |
2004年 | 12篇 |
2003年 | 17篇 |
2002年 | 12篇 |
2001年 | 21篇 |
2000年 | 16篇 |
1999年 | 26篇 |
1998年 | 72篇 |
1997年 | 82篇 |
1996年 | 58篇 |
1995年 | 52篇 |
1994年 | 37篇 |
1993年 | 44篇 |
1992年 | 14篇 |
1991年 | 9篇 |
1990年 | 12篇 |
1989年 | 26篇 |
1988年 | 22篇 |
1987年 | 27篇 |
1986年 | 14篇 |
1985年 | 17篇 |
1984年 | 11篇 |
1983年 | 12篇 |
1982年 | 10篇 |
1981年 | 8篇 |
1980年 | 9篇 |
1978年 | 5篇 |
1977年 | 11篇 |
1976年 | 5篇 |
1975年 | 2篇 |
1934年 | 1篇 |
1931年 | 1篇 |
1930年 | 1篇 |
排序方式: 共有1194条查询结果,搜索用时 15 毫秒
11.
Astrid LA. Kuijpers Rolph Pfundt Patrick LJM Zeeuwen Henri OF. Molhuizen Edwin CM. Mariman Peter CM. van de Kerkhof Joost Schalkwijk 《Clinical genetics》1998,54(1):96-101
Psoriasis is a multifactorial skin disease characterised by epidermal abnormalities and infiltration by lymphocytes and polymorphonuclear leukocytes (PMN). Skin-derived antileukoproteinase (SKALP), also known as elafin, is a potent inhibitor of human leukocyte elastase and proteinase 3, two PMN-derived proteinases implicated in tissue destruction and leukocyte migration. We have shown that, at least at the protein level, SKALP is significantly decreased in lesional skin of patients with pustular psoriasis compared with plaque-type psoriasis. This finding raised the possibility that SKALP could be one of the candidate genes for pustular forms of psoriasis. We therefore performed single strand conformation polymorphism (SSCP) analysis on the SKALP gene to screen for mutations/polymorphisms in the exons of 30 patients with plaque-type psoriasis, 15 patients with pustular psoriasis and 48 healthy controls. In exon 1 a polymorphism was detected at position + 43 relative to the translation start site, resulting in a substitution of threonine for alanine in the signal peptide. In the promoter region a dinucleotide repeat polymorphism was identified. Both polymorphisms were not associated with pustular psoriasis, or psoriasis in general. Our data indicate that the decrease in SKALP activity in pustular psoriasis is not caused by mutations in the coding region of the gene, and that there is no allelic association between pustular psoriasis and SKALP gene polymorphisms. 相似文献
12.
Dal Zotto L; Quaderi NA; Elliott R; Lingerfelter PA; Carrel L; Valsecchi V; Montini E; Yen CH; Chapman V; Kalcheva I; Arrigo G; Zuffardi O; Thomas S; Willard HF; Ballabio A; Disteche CM; Rugarli EI 《Human molecular genetics》1998,7(3):489-499
We have recently reported isolation of the gene responsible for X- linked
Opitz G/BBB syndrome, a defect of midline development. MID1 is located on
the distal short arm of the human X chromosome (Xp22. 3) and encodes a
novel member of the B box family of zinc finger proteins. We have now
cloned the murine homolog of MID1 and performed preliminary expression
studies during development. Mid1 expression in undifferentiated cells in
the central nervous, gastrointestinal and urogenital systems suggests that
abnormal cell proliferation may underlie the defect in midline development
characteristic of Opitz syndrome. We have also found that Mid1 is located
within the mouse pseudoautosomal region (PAR) in Mus musculus , while it
seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a
recent acquisition of the M. musculus PAR. Genetic and FISH analyses also
demonstrated a high frequency of unequal crossovers in the murine PAR,
creating spontaneous deletion/duplication events involving Mid1. These data
provide evidence for the first time that genetic instability of the PAR may
affect functionally important genes. In addition, we show that MID1 is the
first example of a gene subject to X-inactivation in man while escaping it
in mouse. These data contribute to a better understanding of the molecular
content and evolution of the rodent PAR.
相似文献
13.
L Ozzello CM De Rosa EW Blank K Cantell RL Ceriani DV Habif Sr 《Breast cancer research and treatment》1993,25(3):265-276
Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of125I-nIFN/Mc5 by the tumors was greater and its elimination slower than for125I-nIFN alone or conjugated to irrelevant mouse IgG1. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy. 相似文献
14.
To find out the efficacy of sucralfate in preventing gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective, randomised single blind study was conducted from 1989 to 1992. Patients with osteoarthritis, rheumatoid arthritis and other long standing painful conditions, who were expected to receive NSAIDs for over three months, were recruited into the study. All medicines were discontinued for a period of 10–15 days prior to initial endoscopic assessment. NSAID therapy was started and the patients were randomised to receive either placebo (group A) or sucralfate (group B) in addition. Patient were reassessed clinically every week and an endoscopic examination was repeated after 6–8 weeks of follow-up. A total of 176 patients were studied in group A (n=91) and group B (n=85). At the end of 8 weeks gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and B respectively. Endoscopic assessment showed superficial lesions in 36.5% and 18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B respectively. Thus in patients receiving chronic NSAID therapy, simultaneous administration of sucralfate reduces the incidence of superficial gastric lesions but has no significant effect on symptoms or ulcer formation.KEY WORDS: Gastropathy, Sucralfate, Nonsteroidal anti-inflammatory drugs 相似文献
15.
BACKGROUND: Despite an increased awareness among clinicians regarding pain and pain management for infants undergoing surgery, pain associated with procedures performed outside the operating room may not be adequately managed. PURPOSE: To examine the beliefs and self-described behavior of physicians and nurses regarding the management of procedural pain in newborn infants. METHODS: A survey was distributed to 467 clinicians (nurses and physicians) working in 11 level II and 4 level III nurseries in a large metropolitan area. Respondents were asked to rate the painfulness of 12 common bedside nursery procedures and how often pharmacologic and nonpharmacologic (comfort) measures are currently used and should be used for those procedures. Demographic data were also collected. RESULTS: Surveys were completed by 374 clinicians (80% response rate). Physicians and nurses believe infants feel as much pain as adults and that 9 of the 12 listed procedures are moderately to very painful. Neither pharmacologic nor comfort measures are believed to be used frequently, even for the most painful procedures. Physicians and nurses believe both pharmacologic and comfort measures should be used more frequently, but nurses believe comfort measures should be used more frequently than do physicians. Beliefs about infant pain and procedural pain were related to pain management preferences. Physicians' but not nurses' ratings were associated with significant personal pain. CONCLUSIONS: Despite their beliefs that infants experience significant procedure-related pain, clinicians believe pain management for infants remains below optimal levels. Barriers to more consistent and effective pain management need to be identified and surmounted. 相似文献
16.
17.
An Australian study of functional status after childbirth 总被引:1,自引:0,他引:1
18.
19.
Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog 总被引:8,自引:0,他引:8
Inactivation of the p53 tumor suppressor gene has been implicated in the
pathogenesis of numerous human cancers, including osteosarcomas.
Appendicular osteosarcomas of the dog appear to be a good model for their
human equivalent with regard to biologic behavior, epidemiology and
histopathology. We individually screened exons 5-8 of the p53 gene for
mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to
compare the role of this gene in human and canine osteosarcoma
tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with
one tumor possessing two mutations within different exons. Of these, seven
were missense mutations and the eighth was a 'silent' mutation potentially
affecting the exon 6-7 splicing region. Five of the missense mutations were
located in highly conserved regions IV and V, while another corresponded
with the highly conserved codon 220 mutational hotspot located outside the
conserved domains. The locations and types of mutations were nearly
identical to those reported in human cancer. These findings provide strong
evidence of the involvement of p53 mutations in the development of canine
appendicular osteosarcomas. Canine osteosarcomas appear to be a promising
model for their human equivalent on a clinical, pathologic, and molecular
level.
相似文献
20.
Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer 总被引:2,自引:0,他引:2
Davidson LA; Aymond CM; Jiang YH; Turner ND; Lupton JR; Chapkin RS 《Carcinogenesis》1998,19(2):253-257
We have developed a non-invasive method utilizing feces, containing
sloughed colonocytes, as a sensitive technique for detecting diagnostic
colonic biomarkers. In this study, we used the rat colon carcinogenesis
model to determine if changes in fecal protein kinase C (PKC) expression
have predictive value in monitoring the neoplastic process. Weanling rats
were injected with saline or azoxymethane (AOM) and 36 weeks later fecal
samples and mucosa were collected, poly A+ RNA isolated, and quantitative
RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and
zeta mRNA levels were altered by the presence of a tumor, with
tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII
expression as compared with animals without tumors. In addition,
AOM-injection increased mucosal PKC betaII mRNA expression compared with
saline controls. No effect of tumor incidence on mucosal PKC betaII
expression was observed. In contrast, fecal PKC zeta expression was
2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus
saline. Since tumor incidence exerts a reciprocal effect on fecal PKC
betaII and zeta mRNA expression, data were also expressed as the ratio
between PKC betaII and zeta. The isozyme ratio was strongly related to
tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25,
animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that
the expression of fecal PKC betaII and zeta may serve as a noninvasive
marker for development of colon tumors. A sensitive technique for the
detection of colon cancer is of importance since early diagnosis can
substantially reduce mortality.
相似文献