全文获取类型
收费全文 | 1366篇 |
免费 | 123篇 |
国内免费 | 28篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 83篇 |
妇产科学 | 18篇 |
基础医学 | 175篇 |
口腔科学 | 57篇 |
临床医学 | 179篇 |
内科学 | 253篇 |
皮肤病学 | 19篇 |
神经病学 | 57篇 |
特种医学 | 300篇 |
外科学 | 109篇 |
综合类 | 22篇 |
预防医学 | 91篇 |
眼科学 | 6篇 |
药学 | 82篇 |
肿瘤学 | 61篇 |
出版年
2021年 | 7篇 |
2019年 | 7篇 |
2018年 | 22篇 |
2017年 | 12篇 |
2016年 | 14篇 |
2015年 | 21篇 |
2014年 | 24篇 |
2013年 | 34篇 |
2012年 | 28篇 |
2011年 | 35篇 |
2010年 | 39篇 |
2009年 | 29篇 |
2008年 | 28篇 |
2007年 | 52篇 |
2006年 | 40篇 |
2005年 | 29篇 |
2004年 | 33篇 |
2003年 | 42篇 |
2002年 | 30篇 |
2001年 | 22篇 |
2000年 | 28篇 |
1999年 | 28篇 |
1998年 | 70篇 |
1997年 | 73篇 |
1996年 | 83篇 |
1995年 | 51篇 |
1994年 | 42篇 |
1993年 | 48篇 |
1992年 | 34篇 |
1991年 | 22篇 |
1990年 | 35篇 |
1989年 | 52篇 |
1988年 | 48篇 |
1987年 | 41篇 |
1986年 | 40篇 |
1985年 | 47篇 |
1984年 | 21篇 |
1983年 | 22篇 |
1982年 | 16篇 |
1981年 | 19篇 |
1980年 | 13篇 |
1979年 | 14篇 |
1978年 | 13篇 |
1977年 | 17篇 |
1976年 | 19篇 |
1975年 | 8篇 |
1974年 | 4篇 |
1973年 | 7篇 |
1966年 | 4篇 |
1915年 | 4篇 |
排序方式: 共有1517条查询结果,搜索用时 62 毫秒
31.
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
32.
Mahadevaiah SK; Odorisio T; Elliott DJ; Rattigan A; Szot M; Laval SH; Washburn LL; McCarrey JR; Cattanach BM; Lovell-Badge R; Burgoyne PS 《Human molecular genetics》1998,7(4):715-727
An RNA-binding motif (RBM) gene family has been identified on the human Y
chromosome that maps to the same deletion interval as the 'azoospermia
factor' (AZF). We have identified the homologous gene family (Rbm) on the
mouse Y with a view to investigating the proposal that this gene family
plays a role in spermatogenesis. At least 25 and probably >50 copies of
Rbm are present on the mouse Y chromosome short arm located between Sry and
the centromere. As in the human, a role in spermatogenesis is indicated by
a germ cell-specific pattern of expression in the testis, but there are
distinct differences in the pattern of expression between the two species.
Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are
female due to a position effect resulting in non-expression of Sry ;
sex-reversing such mice with an Sry transgene produces males with a high
incidence of abnormal sperm, making this the third deletion interval on the
mouse Y that affects some aspect of spermatogenesis. Most of the copies of
Rbm map to this deletion interval, and the Yd1males have markedly reduced
Rbm expression, suggesting that RBM deficiency may be responsible for, or
contribute to, the abnormal sperm development. In man, deletion of the
functional copies of RBM is associated with meiotic arrest rather than
sperm anomalies; however, the different effects of deletion are consistent
with the differences in expression between the two species.
相似文献
33.
ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome 总被引:11,自引:3,他引:11
Picketts DJ; Higgs DR; Bachoo S; Blake DJ; Quarrell OW; Gibbons RJ 《Human molecular genetics》1996,5(12):1899-1907
It was shown recently that mutations of the ATRX gene give rise to a
severe, X-linked form of syndromal mental retardation associated with alpha
thalassaemia (ATR-X syndrome). In this study, we have characterised the
full-length cDNA and predicted structure of the ATRX protein. Comparative
analysis shows that it is an entirely new member of the SNF2 subgroup of a
superfamily of proteins with similar ATPase and helicase domains. ATRX
probably acts as a regulator of gene expression. Definition of its genomic
structure enabled us to identify four novel splicing defects by screening
52 affected individuals. Correlation between these and previously
identified mutations with variations in the ATR-X phenotype provides
insights into the pathophysiology of this disease and the normal role of
the ATRX protein in vivo.
相似文献
34.
Bettina H Clausen Kate L Lambertsen Alicia A Babcock Thomas H Holm Frederik Dagnaes-Hansen Bente Finsen 《Journal of neuroinflammation》2008,5(1):46
Background
Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1β is primarily neurotoxic in ischemic stroke, TNF-α may have neurotoxic and/or neuroprotective effects. We investigated whether IL-1β and TNF-α are synthesized by overlapping or segregated populations of cells after ischemic stroke in mice. 相似文献35.
DJ SINGH 《Medical Journal Armed Forces India》1996,52(4):239-241
Stress fractures amongst military recruits are limited to the lower extremities; yet involvement of the shaft of the femur is unusual. Seven such cases in a series of 352 stress fractures are presented. The importance of early recognition and management is emphasized with a view to prevent bony disruption in an otherwise easily treatable condition.KEY WORDS: Fractures stress, Femoral fractures 相似文献
36.
MA Ebert J Blight S Price A Haworth C Hamilton D Cornes DJ Joseph 《Journal of Medical Imaging and Radiation Oncology》2004,48(3):347-352
Digital data from 3‐D treatment planning computers is generally used for patient planning and then never considered again. However, such data contains enormous quantities of information regarding patient geometries, tissue outlining, treatment approaches and dose distributions. Were such data accessible from planning systems from multiple manufacturers, there would be substantial opportunities for undertaking quality assurance of radiotherapy clinical trials, prospective assessment of trial outcomes and basic treatment planning research and development. The technicalities of data exchange between planning systems are outlined, and previous attempts at producing systems capable of viewing and/or manipulating imaging and radiotherapy digital data reviewed. Development of a software system for enhancing the quality of Australasian clinical trials is proposed. 相似文献
37.
Nutritional immunomodulation leads to enhanced allograft survival in combination with cyclosporine A and rapamycin, but not FK506 总被引:1,自引:0,他引:1
Gibson SW Valente JF Alexander JW Custer DA Li BG Frede S Babcock GF Ogle CK 《Transplantation》2000,69(10):2034-2038
BACKGROUND: Recently, specific immunonutrients were found to increase experimental allograft survival when combined with cyclosporine A (CsA). This study compared the effect on rat cardiac allograft survival when nutritional immunomodulation was used with CsA, rapamycin (Rapa), or tacrolimus (FK506). METHODS: Intra-abdominal ACI to Lewis cardiac allografts were performed and assessed daily by palpation. Study groups included untreated controls and those receiving CsA, Rapa, or FK506. Rats were fed ad libitum with Impact diet (fortified with fish oil, arginine, and RNA) or standard rat food. Further study groups were transplanted that received a donor-specific transfusion in addition to immunosuppression and diet. RESULTS: Allograft survival was extended by combining Impact with CsA (45.3+/-19 days) and Rapa (165.3+/-52 days), but not FK506 (12.4+/-3.2 days). Mean graft survival in the Rapa/Impact group met criteria for functional tolerance. The addition of a donor-specific transfusion did not lead to graft survival advantages over similar groups not receiving a donor-specific transfusion. CONCLUSIONS: The use of immunonutrients improves transplant outcome in animals treated with short courses of CsA and Rapa, but not FK506. These findings highlight the potential differences in the effects of nutritional immunomodulation with different immunosuppressive drugs in the treatment of transplant patients. 相似文献
38.
S Bydder NA Spry DRH Christie D Roos BH Burmeister H Krawitz S Davis DJ Joseph M Poulsen M Berry 《Journal of Medical Imaging and Radiation Oncology》2003,47(3):284-288
The purpose of this study was to prospectively examine the effectiveness and tolerability of a simple radiotherapy technique for the palliation of symptomatic liver metastases. Twenty‐eight patients with symptomatic liver metastases were enrolled from seven centres, and received targeted (partial or whole) liver irradiation consisting of 10 Gy in two fractions over 2 days. Symptoms at baseline were hepatic pain (27 patients), abdominal distension (19), night sweats (12), nausea (18) and vomiting (eight). Twenty‐two patients (76%) had failed previous treatment with chemotherapy, hormonal therapy and/or high‐dose steroids. Symptoms and potential toxicities were prospectively assessed at the time of treatment, then 2, 6 and 10 weeks later. Individual symptom response rates were 53?66% at 2 weeks. Partial or complete global symptomatic responses were noted in 15 patients (54%) overall. The treatment was well tolerated with two patients (7%) experiencing grade 3 toxicity (one vomiting and one diarrhoea); however, four patients reported temporary worsening of pain shortly after treatment. This simple and well‐tolerated treatment achieves useful palliation. 相似文献
39.
Neuronal apoptosis after CNS injury: the roles of glutamate and calcium 总被引:16,自引:0,他引:16
While a role has been well established for excitotoxic necrosis in the pathogenesis of traumatic or ischemic damage to the CNS, accumulating evidence now suggests that apoptosis may also be a prominent contributor. In this review we focus on the role of glutamate and attendant intracellular calcium influx in triggering or modifying excitotoxic necrosis and apoptosis, raising the possibility that calcium influx may affect these two death pathways in opposite directions. Incorporating consideration of both pathways will probably be needed to develop the most effective neuroprotective treatments for CNS injury. 相似文献
40.
Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method 总被引:2,自引:0,他引:2
Objective : The aim of this study was to investigate the inter-relationship between urinary excretion of alpha-1-microglobulin (AIM), retinol-binding protein (RBP) and albumin in term and premature neonates, with urine collected into cotton wool balls and extracted by a novel method. Subjects and methods : Sixty-four infants were studied on the first day of life; 26 had been born at term (37–42 weeks gestation) and 38 prematurely (24–28 weeks n = 16, 29–36 weeks n = 22). Urine collected into cotton wool balls was analysed following a new detergent extraction method, which resulted in a recovery rate of 94–107% for albumin, AIM, RBP and creatinine. Results : Urinary protein excretion, expressed as a ratio to urinary creatinine, decreased significantly with increasing gestational age (24–28 weeks, 29–36 weeks, 37–42 weeks: albuminxreatinine ratio mg/mmol mean 96.9, 31.7, 19.3; AIM: creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP: creatinine ratio mg/mmol mean 16.2, 3.8, and <0.01, below the limit of detection, respectively). When results were corrected for birthweight, this gestation-associated effect was still present for A1M and RBP, but not for albumin. In premature infants there was a significant positive correlation between AIM: creatinine ratio and RBP: creatinine ratio ( r = 0.85), and also between albumin and both AIM and RBP ( r = 0.82 and 0.77). Conclusion : Increased excretion of AIM, RBP and albumin at earlier gestational ages is probably due to proximal tubular immaturity, although tubular damage and also glomerular dysfunction cannot be excluded as possible explanations. 相似文献