全文获取类型
收费全文 | 620篇 |
免费 | 44篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 49篇 |
妇产科学 | 4篇 |
基础医学 | 37篇 |
口腔科学 | 24篇 |
临床医学 | 74篇 |
内科学 | 157篇 |
皮肤病学 | 2篇 |
神经病学 | 10篇 |
特种医学 | 147篇 |
外科学 | 27篇 |
综合类 | 30篇 |
预防医学 | 36篇 |
眼科学 | 2篇 |
药学 | 24篇 |
肿瘤学 | 41篇 |
出版年
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 9篇 |
2017年 | 7篇 |
2016年 | 9篇 |
2015年 | 14篇 |
2014年 | 22篇 |
2013年 | 22篇 |
2012年 | 13篇 |
2011年 | 4篇 |
2010年 | 12篇 |
2009年 | 8篇 |
2008年 | 13篇 |
2007年 | 16篇 |
2006年 | 13篇 |
2005年 | 19篇 |
2004年 | 21篇 |
2003年 | 13篇 |
2002年 | 21篇 |
2001年 | 14篇 |
2000年 | 13篇 |
1999年 | 27篇 |
1998年 | 30篇 |
1997年 | 33篇 |
1996年 | 42篇 |
1995年 | 31篇 |
1994年 | 32篇 |
1993年 | 24篇 |
1992年 | 9篇 |
1991年 | 11篇 |
1990年 | 8篇 |
1989年 | 16篇 |
1988年 | 20篇 |
1987年 | 18篇 |
1986年 | 20篇 |
1985年 | 15篇 |
1984年 | 10篇 |
1983年 | 13篇 |
1982年 | 4篇 |
1981年 | 10篇 |
1980年 | 7篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 3篇 |
排序方式: 共有669条查询结果,搜索用时 15 毫秒
31.
Day DJ; Speiser PW; Schulze E; Bettendorf M; Fitness J; Barany F; White PC 《Human molecular genetics》1996,5(12):2039-2048
Steroid 21-hydroxylase deficiency is among the most common inborn errors of
metabolism in man. Characterization of mutations in the 21- hydroxylase
gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase
chain reaction (PCR). The most common mutation is conversion of an A or C
at nt656 to a G in the second intron causing aberrant splicing of mRNA.
Homozygosity for nt656G is associated with profoundly deficient adrenal
cortisol and aldosterone synthesis, secondary hypersecretion of adrenal
androgens, and a severe form of congenital adrenal hyperplasia (CAH)
characterized by ambiguous genitalia and/or sodium wasting in newborns.
During the course of genetic analysis of CYP21 mutations in CAH families,
we and others have noticed a number of relatives genotyped as nt656G
homozygotes, yet showing no clinical signs of disease. A number of lines of
evidence have led us to propose that the putative asymptomatic nt656G/G
individuals are incorrectly typed due to dropout of one haplotype during
PCR amplification of CYP21. For prenatal diagnosis, we recommend that
microsatellite typing be used as a supplement to CYP21 genotyping in order
to resolve ambiguities at nt656.
相似文献
32.
Excessive dorsiflexion (dorsal tilting) of the lunate on a lateral wrist radiograph can be an important sign of carpal injury. Lunate dorsiflexion is a well-recognized sign of an intercarpal ligamentous injury pattern known as dorsal intercalated segment instability (DISI). It is less well recognized that excessive dorsal tilting of the lunate (DISI configuration) can also be produced by displacement of a scaphoid waist fracture. Since the management and prognosis of displaced scaphoid fractures may be quite different from those for nondisplaced fractures, radiologists can make an important contribution by recognizing dorsal tilting of the lunate and appreciating that it may be an important, indirect sign of scaphoid fracture displacement, which may not be directly visualized with standard wrist radiography. In this setting, computed tomography or complex motion tomography may be helpful for further evaluation of the scaphoid fracture. 相似文献
33.
Ingo Helbig Marielle E M Swinkels Emmelien Aten Almuth Caliebe Ruben van 't Slot Rainer Boor Sarah von Spiczak Hiltrud Muhle Johanna A J?hn Ellen van Binsbergen Onno van Nieuwenhuizen Floor E Jansen Kees P J Braun Gerrit-Jan de Haan Niels Tommerup Ulrich Stephani Helle Hjalgrim Martin Poot Dick Lindhout Eva H Brilstra Rikke S M?ller Bobby PC Koeleman 《European journal of human genetics : EJHG》2014,22(7):896-901
A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies. 相似文献
34.
Thirty-eight infected pancreatic fluid collections in 23 patients with acute or chronic pancreatitis were drained percutaneously following initial diagnosis with computed tomography and fine-needle aspiration. Fifteen (65.2%) patients were cured completely without surgery. Eight (34.8%) patients required some type of surgery despite successful treatment of the fluid collection, and in two (6.5%) the collection recurred after catheter removal. Complications occurred in three (13%) patients, but only one complication (4%), empyema, was a direct result of catheter drainage. Catheter drainage time averaged 29 days for 16 patients with isolated collections and 96 days and 104 days for patients with collections with pancreatic duct fistulas (nine patients) or gastrointestinal fistulas (14 patients), respectively. This study confirms that infected pancreatic fluid collections can be safely and effectively treated with percutaneous catheter techniques in most patients. 相似文献
35.
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis 总被引:5,自引:0,他引:5
Maheshwar MM; Cheadle JP; Jones AC; Myring J; Fryer AE; Harris PC; Sampson JR 《Human molecular genetics》1997,6(11):1991-1996
Tuberous sclerosis is an autosomal dominant trait in which the
dysregulation of cellular proliferation and differentiation results in the
development of hamartomatous growths in many organs. The TSC2 gene is one
of two genes determining tuberous sclerosis. Inactivating germline
mutations of TSC2 in patients with tuberous sclerosis and somatic loss of
heterozygosity at the TSC2 locus in the associated hamartomas indicate that
TSC2 functions as a tumour suppressor gene and that loss of function is
critical to expression of the tuberous sclerosis phenotype. The TSC2
product, tuberin, has a region of homology with the GTPase activating
protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in
vitro. Here we show that the region of homology between tuberin and human
rap1GAP and the murine GAP mSpa1 is more extensive than previously reported
and spans approximately 160 amino acid residues encoded within exons 34-38
of the TSC2 gene. Single strand conformation polymorphism analysis of these
exons in 173 unrelated patients with tuberous sclerosis and direct
sequencing of variant conformers together with study of additional family
members enabled characterisation of disease associated mutations in 14
cases. Missense mutations, which occurred in exons 36, 37 and 38 were
identified in eight cases, four of whom shared the same recurrent change
P1675L. Each of the five different missense mutations identified was shown
to occur de novo in at least one sporadic case of tuberous sclerosis. The
high proportion of missense mutations detected in the region of the TSC2
gene encoding the GAP-related domain supports its key role in the
regulation of cellular growth.
相似文献
36.
PC Ng J Hiu TF Fok EAS Nelson KL Cheung W Wong 《Acta paediatrica (Oslo, Norway : 1992)》1995,84(8):955-956
We report an unusual case of localized congenital tuberculosis otitis in a preterm infant. Unlike disseminated congenital cases, the manifestations of localized otitis are associated with a triad of signs: (i) regional lymphadenopathy in the absence of typical systemic features of tuberculosis; (ii) delayed onset of presentation; and (iii) refractory otitis unresponsive to conventional antimicrobial agents. The need for greater diligence in looking for neonatal tuberculosis is emphasized, especially in an ethnic or socioeconomic environment where the disease is prevalent. Congenital tuberculosis, otitis, preterm
PC Ng, Department of Paediatrics, Level 6, Clinical Sciences Building, Prince of Wales Hospital, Shatin, NT, Hong Kong 相似文献
PC Ng, Department of Paediatrics, Level 6, Clinical Sciences Building, Prince of Wales Hospital, Shatin, NT, Hong Kong 相似文献
37.
Norton KI Kattan M Rao JS Cleveland R Trautwein L Mellins RB Berdon W Boechat MI Wood B Meziane M Platzker AC;P 《AJR. American journal of roentgenology》2001,176(6):1553-1558
OBJECTIVE: We prospectively studied children with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 to determine the incidence of chronic radiographic lung changes (CRC) and to correlate these changes with clinical assessments. SUBJECTS AND METHODS: Between 1990 and 1997, we scored 3050 chest radiographs using a standardized form. Group I children (n = 201) were HIV-1-infected at enrollment. Group II children (n = 512) were enrolled prenatally or before 28 days postpartum and subsequently subdivided into group IIa (n = 86), children identified as HIV-1-infected; and group IIb (n = 426), those who were HIV-1-uninfected. CRC were defined as parenchymal consolidations or nodular disease lasting 3 months or more or increased bronchovascular markings or reticular densities lasting 6 months or more. Morbidity was assessed by CD4 counts, viral load, the presence of low oxygen saturation, wheezing, tachypnea, crackles, and clubbing. RESULTS: The cumulative incidence of chronic radiographic lung changes in HIV-1-infected children was 32.8% by 4 years old, with increased bronchovascular markings or reticular densities being most common. Chronic changes were associated with lower CD4 cell counts and higher viral loads. Resolution of these chronic changes was associated with decreasing CD4 cell counts but not with lower rates of clinical findings, viral load, or difference in survival. CONCLUSION: With increased survival, CRC are becoming more common. The resolution of these changes may indicate immunologic deterioration rather than clinical improvement. 相似文献
38.
Biomarkers for lysosomal storage disorders: identification and application as exemplified by chitotriosidase in Gaucher disease 总被引:1,自引:0,他引:1
Johannes M Aerts Marielle J van Breemen Anton P Bussink Karen Ghauharali Richard Sprenger Rolf G Boot Johanna E Groener Carla E Hollak Mario Maas Suzanne Smit Huub C Hoefsloot Age K Smilde Johannes PC Vissers Sheryas de Jong Dave Speijer Chris G de Koster 《Acta paediatrica (Oslo, Norway : 1992)》2008,97(S457):7-14
39.
Wang JF; Bashir M; Engelsberg BN; Witmer C; Rozmiarek H; Billings PC 《Carcinogenesis》1997,18(2):371-375
Chromium (Cr) is a human carcinogen and a potent DNA damaging agent.
Incubation of DNA with CrCl3 resulted in dose-dependent binding of Cr to
DNA and, at concentrations >20 microM, altered the electrophoretic
mobility of a 100 bp oligonucleotide. We also demonstrate that high
mobility group (HMG) proteins 1 and 2 bind Cr-damaged DNA (Cr-DNA). Protein
binding was lesion density-dependent, with maximal binding to DNA treated
with 100 microM CrCl3. HMG2 binds to Cr-DNA with a calculated Kd of
approximately 10(-9) M. These proteins also bound DNA obtained from
chromate-treated cells. These results suggest that the covalent attachment
of Cr to DNA induces alterations in DNA structure which are recognized by
HMG1 and HMG2. Therefore, these proteins may function as Cr-damaged DNA
recognition proteins in vivo and as a consequence of binding, may play a
role in directing the cellular response to Cr-DNA adduct formation.
相似文献
40.