全文获取类型
收费全文 | 1260篇 |
免费 | 202篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 15篇 |
儿科学 | 93篇 |
妇产科学 | 14篇 |
基础医学 | 94篇 |
口腔科学 | 39篇 |
临床医学 | 158篇 |
内科学 | 527篇 |
皮肤病学 | 9篇 |
神经病学 | 39篇 |
特种医学 | 164篇 |
外科学 | 137篇 |
综合类 | 46篇 |
预防医学 | 49篇 |
眼科学 | 1篇 |
药学 | 34篇 |
中国医学 | 5篇 |
肿瘤学 | 48篇 |
出版年
2022年 | 3篇 |
2021年 | 11篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 35篇 |
2017年 | 42篇 |
2016年 | 37篇 |
2015年 | 34篇 |
2014年 | 36篇 |
2013年 | 62篇 |
2012年 | 30篇 |
2011年 | 30篇 |
2010年 | 65篇 |
2009年 | 57篇 |
2008年 | 45篇 |
2007年 | 60篇 |
2006年 | 43篇 |
2005年 | 41篇 |
2004年 | 24篇 |
2003年 | 25篇 |
2002年 | 20篇 |
2001年 | 26篇 |
2000年 | 19篇 |
1999年 | 16篇 |
1998年 | 63篇 |
1997年 | 58篇 |
1996年 | 62篇 |
1995年 | 54篇 |
1994年 | 34篇 |
1993年 | 46篇 |
1992年 | 30篇 |
1991年 | 31篇 |
1990年 | 30篇 |
1989年 | 28篇 |
1988年 | 39篇 |
1987年 | 35篇 |
1986年 | 31篇 |
1985年 | 19篇 |
1984年 | 17篇 |
1983年 | 22篇 |
1982年 | 6篇 |
1981年 | 21篇 |
1980年 | 13篇 |
1979年 | 8篇 |
1978年 | 5篇 |
1977年 | 12篇 |
1976年 | 14篇 |
1975年 | 8篇 |
1972年 | 3篇 |
1971年 | 2篇 |
排序方式: 共有1472条查询结果,搜索用时 15 毫秒
21.
Marjolein P de Vries Lisette van den Bemt Karen Aretz Bart PA Thoonen Jean WM Muris Arnold DM Kester Sonja Cloosterman CP Onno van Schayck 《The British journal of general practice》2007,57(536):184-190
BACKGROUND: The efficacy of bed covers that are impermeable to house dust mites has been disputed. AIM: The aim of the present study was to investigate whether the combination of 'house dust mite impermeable' covers and a self-management plan, based on peak flow values and symptoms, leads to reduced use of inhaled corticosteroids (ICS) than self-management alone. DESIGN OF STUDY: Prospective, randomised, double blind, placebo-controlled trial. SETTING: Primary care in a south-eastern region of the Netherlands. METHOD: Asthma patients aged between 16 and 60 years with a house dust mite allergy requiring ICS were randomised to intervention and placebo groups. They were trained to use a self-management plan based on peak flow and symptoms. After a 3-month training period, the intervention commenced using house dust mite impermeable and placebo bed covers. The follow-up period was 2 years. Primary outcome was the use of ICS; secondary outcomes were peak expiratory flow parameters, asthma control, and symptoms. RESULTS: One hundred and twenty-six patients started the intervention with house dust mite impermeable or placebo bed covers. After 1 and 2 years, significant differences in allergen exposure were found between the intervention and control groups (P<0.001). No significant difference between the intervention and control groups was found in the dose of ICS (P = 0.08), morning peak flow (P = 0.52), peak flow variability (P = 0.36), dyspnoea (P = 0.46), wheezing (P = 0.77), or coughing (P = 0.41). There was no difference in asthma control between the intervention and control groups. CONCLUSION: House dust mite impermeable bed covers combined with self-management do not lead to reduced use of ICS compared with self-management alone. 相似文献
22.
Tissue and lineage-specific variation in inactive X chromosome expression of the murine Smcx gene 总被引:2,自引:0,他引:2
To understand how gene expression patterns are established on the inactive
X chromosome during development, we have studied the murine gene Smcx,
which is expressed from both the active and inactive mouse X chromosomes.
In all tissues assayed, Smcx only partially escapes X inactivation, with
expression levels from the inactive X allele approximately 30-65% that of
the active X allele. Additionally, inactive X expression levels differed
between extraembryonic and embryonic tissues and among different tissues
from newborn and adult mice. Imprinted extraembryonic tissue had the lowest
levels of inactive X Smcx expression, whereas the highest levels were in
heart. These data suggest that the chromosomal basis of X inactivation
differs among tissues, perhaps reflecting differences in the timing or
regulation of inactivation in these cell lineages.
相似文献
23.
George N Papanikolaou Maria S Baltogianni Despina G Contopoulos-Ioannidis Anna-Bettina Haidich Ioannis A Giannakakis John PA Ioannidis 《BMC medical research methodology》2001,1(1):3
Background
Guidelines published in major medical journals are very influential in determining clinical practice. It would be essential to evaluate whether conflicts of interests are disclosed in these publications. We evaluated the reporting of conflicts of interest and the factors that may affect such disclosure in a sample of 191 guidelines on therapeutic and/or preventive measures published in 6 major clinical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, New England Journal of Medicine, Pediatrics) in 1979, 1984, 1989, 1994 and 1999.Results
Only 7 guidelines (3.7%) mentioned conflicts of interest and all were published in 1999 (17.5% (7/40) of guidelines published in 1999 alone). Reporting of conflicts of interest differed significantly by journal (p=0.026), availability of disclosure policy by the journal (p=0.043), source of funding (p < 0.001) and number of authors (p=0.004). In the entire database of 191 guidelines, a mere 18 authors disclosed a total of 24 potential conflicts of interest and most pertained to minor issues.Conclusions
Despite some recent improvement, reporting of conflicts of interest in clinical guidelines published in influential journals is largely neglected.24.
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
25.
A model of corrective gene transfer in X-linked ichthyosis 总被引:5,自引:0,他引:5
Freiberg RA; Choate KA; Deng H; Alperin ES; Shapiro LJ; Khavari PA 《Human molecular genetics》1997,6(6):927-933
Single gene recessive genetic skin disorders offer attractive prototypes
for the development of therapeutic cutaneous gene delivery. We have
utilized X-linked ichthyosis (XLI), characterized by loss of function of
the steroid sulfatase arylsulfatase C (STS), to develop a model of
corrective gene delivery to human skin in vivo. A new retroviral expression
vector was produced and utilized to effect STS gene transfer to primary
keratinocytes from XLI patients. Transduction was associated with
restoration of full-length STS protein expression as well as steroid
sulfatase enzymatic activity in proportion to the number of proviral
integrations in XLI cells. Transduced and uncorrected XLI keratinocytes,
along with normal controls, were then grafted onto immunodeficient mice to
regenerate full thickness human epidermis. Unmodified XLI keratinocytes
regenerated a hyperkeratotic epidermis lacking STS expression with
defective skin barrier function, effectively recapitulating the human
disease in vivo. Transduced XLI keratinocytes from the same patients,
however, regenerated epidermis histologically indistinguishable from that
formed by keratinocytes from patients with normal skin. Transduced XLI
epidermis demonstrated STS expression in vivo by immunostaining as well as
a normalization of histologic appearance at 5 weeks post-grafting. In
addition, transduced XLI epidermis demonstrated a return of barrier
function parameters to normal. These findings demonstrate corrective gene
delivery in human XLI patient skin tissue at both molecular and functional
levels and provide a model of human cutaneous gene therapy.
相似文献
26.
Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection 总被引:1,自引:17,他引:1
Van Opstal D; Los FJ; Ramlakhan S; Van Hemel JO; Van Den Ouweland AM; Brandenburg H; Pieters MH; Verhoeff A; Vermeer MC; Dhont M; In't Veld PA 《Human reproduction (Oxford, England)》1997,12(4):682-686
Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic
sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome
aberrations including two cases of 47,XXY, four cases involving a 45,X cell
line and three autosomal trisomies. Molecular analysis of the parental
origin of the deleted or supernumerary chromosome was performed by using
polymorphic microsatellite markers. Six cases involving a sex chromosome
abnormality were found to be of paternal origin while the two trisomic
cases that could be analysed were of maternal origin. Two cases involved
the same infertile couple who had two consecutive ICSI pregnancies
terminated because of a chromosome abnormality. The replaced embryos in
both cases originated from a single batch of ICSI fertilized oocytes of
which part was used to initiate the first pregnancy and part was
cryopreserved and used to initiate the second pregnancy.
相似文献
27.
A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy 总被引:6,自引:1,他引:6
Fowler PA; Evans LW; Groome NP; Templeton A; Knight PG 《Human reproduction (Oxford, England)》1998,13(12):3530-3536
Maternal serum concentrations of inhibin-A, inhibin-B, activin-A,
activin-AB, pro-alphaC-related inhibin forms, total follistatin, steroids
and gonadotrophins were measured longitudinally in six normal singleton
pregnancies. Maternal venous blood was collected randomly during a
spontaneous follicular phase prior to donor insemination, at 5, 7, 9, 11,
16, 20, 24, 28, 32 and 36 weeks after the first missed menses and in the
early puerperium. Steroid and gonadotrophin profiles conformed to previous
reports. While at week 5 of gestation inhibin-A, activin-A and follistatin
concentrations were similar to those at the follicular phase, all three
increased progressively (P < 0.001) to maximal concentrations in week
36: approximately 48-fold (3740 +/- 1349 ng inhibin-A/ml), approximately
22-fold (6109 +/- 1443 ng activin-A/ml) and approximately 10-fold (3563 +/-
418 ng follistatin/ml) higher. Pro- alphaC concentrations reached a maximum
in weeks 5 (approximately 5- fold, P < 0.001) and 36 (1027 +/- 174
pg/ml, P < 0.01). Inhibin-B (71 +/- 23 pg/ml prior to pregnancy) was
undetectable (<12 pg/ml) between week 5-16 of gestation but increased
slightly in the third trimester (26 +/- 7 pg/ml in week 36). Activin-AB was
undetectable throughout pregnancy. Post-partum concentrations of inhibin-A
(41 +/- 12 ng/ml), inhibin-B (<12 pg/ml), activin-A (950 +/- 149 pg/ml),
pro-alphaC (128 +/- 22 pg/ml) and follistatin (990 +/- 79 ng/ml) were
substantially lower than at week 36 of gestation. The activin-A:follistatin
ratio increased from 0.5 in week 5 to 1.8 in week 36, suggesting that more
free activin-A is available in the maternal circulation during late
pregnancy.
相似文献
28.
KM Kanal NJ Hangiandreou AM Sykes HE Eklund PA Araoz JA Leon BJ Erickson 《Journal of digital imaging》2002,14(1):30-37
The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's
gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing
radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers,
and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed
with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant,
and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender
were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women
was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative
English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and
while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology
practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient
way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed
and sensitive manner. 相似文献
29.
S E Harding G Vescovo S M Jones G Bennett M Yacoub P A Poole-Wilson 《The Journal of pathology》1989,159(3):191-196
Isolated single myocytes were prepared from myocardium of developing ventricular aneurysms and from myocardium within the scar of chronic ventricular aneurysms. The morphology and function of the individual cells were compared. The cells from developing aneurysms were rod-shaped, with a distinct sarcomeric structure, but did not contract even in the presence of high calcium concentrations. The sarcomere length was significantly higher than that of cells from chronic aneurysms and approached the theoretical point at which no contraction can occur. Cells from chronic aneurysms were either rod-shaped and contractile, or rounded due to hypercontracture of the myofilaments. Electron microscopy of cells from developing aneurysms confirmed the presence of elongated sarcomeres, a loss of the actin-myosin interdigitation, and damage to the contractile proteins which was particularly evident in the thin filaments. Cells with similar characteristics have also been isolated from a ruptured, ischaemic papillary muscle. These changes, which are due either to ischaemia or to overstretching of cells, may account for the weakness of the wall of developing aneurysms and be a cause of rupture or enlargement. 相似文献
30.
Morphological studies have shown that macrophages and microglia undergo
apoptosis in the central nervous system (CNS) in acute experimental
autoimmune encephalomyelitis (EAE) in the Lewis rat. To assess the relative
levels of macrophage and microglial apoptosis, and the molecular mechanisms
involved in this process, we used three-colour flow cytometry to identify
CD45lowCD11b/c+ microglial cells and CD45highCD11b/c+ macrophages in the
inflammatory cells isolated from the spinal cords of Lewis rats 13 days
after immunization with myelin basic protein (MBP) and complete Freund's
adjuvant. Simultaneously, we analyzed the DNA content of these cell
populations to assess the proportions of cells undergoing apoptosis and in
different stages of the cell cycle or examined their expression of three
apoptosis- regulating proteins, i.e. Fas (CD95), Fas ligand (FasL) and
Bcl-2. Microglia were highly vulnerable to apoptosis and were
over-represented in the apoptotic population. Macrophages were less
susceptible to apoptosis than microglia and underwent mitosis more
frequently than microglia. The different susceptibilities of microglia and
macrophages to apoptosis did not appear to be due to variations in Fas,
FasL or Bcl- 2 expression, as the proportions of microglia and macrophages
expressing these proteins were similar, and were relatively high.
Furthermore, in contrast to T cell apoptosis, apoptosis of
microglia/macrophages did not occur more frequently in cells expressing Fas
or FasL, or less frequently in cells expressing Bcl-2. These results
indicate that the apoptosis of microglia and CNS macrophages in EAE is not
mediated through the Fas pathway, and that Bcl-2 expression does not
protect them from apoptosis. Expression of FasL by macrophages and
microglia may contribute to the pathogenesis and immunoregulation of EAE
through interactions with Fas+ oligodendrocytes and Fas+ T cells. The high
level of microglial apoptosis in EAE indicates that microglial apoptosis
may be an important homeostatic mechanism for controlling the number of
microglia in the CNS following microglial activation and proliferation.
相似文献