全文获取类型
收费全文 | 1296篇 |
免费 | 136篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 12篇 |
儿科学 | 97篇 |
妇产科学 | 29篇 |
基础医学 | 170篇 |
口腔科学 | 17篇 |
临床医学 | 148篇 |
内科学 | 229篇 |
皮肤病学 | 13篇 |
神经病学 | 59篇 |
特种医学 | 174篇 |
外科学 | 91篇 |
综合类 | 26篇 |
预防医学 | 171篇 |
眼科学 | 12篇 |
药学 | 140篇 |
中国医学 | 1篇 |
肿瘤学 | 45篇 |
出版年
2021年 | 7篇 |
2019年 | 7篇 |
2018年 | 19篇 |
2017年 | 10篇 |
2016年 | 9篇 |
2015年 | 16篇 |
2014年 | 18篇 |
2013年 | 43篇 |
2012年 | 32篇 |
2011年 | 46篇 |
2010年 | 37篇 |
2009年 | 31篇 |
2008年 | 41篇 |
2007年 | 36篇 |
2006年 | 35篇 |
2005年 | 42篇 |
2004年 | 37篇 |
2003年 | 32篇 |
2002年 | 26篇 |
2001年 | 30篇 |
2000年 | 37篇 |
1999年 | 39篇 |
1998年 | 41篇 |
1997年 | 36篇 |
1996年 | 39篇 |
1995年 | 38篇 |
1994年 | 31篇 |
1993年 | 32篇 |
1992年 | 33篇 |
1991年 | 30篇 |
1990年 | 40篇 |
1989年 | 45篇 |
1988年 | 43篇 |
1987年 | 28篇 |
1986年 | 22篇 |
1985年 | 26篇 |
1984年 | 24篇 |
1983年 | 30篇 |
1982年 | 33篇 |
1981年 | 16篇 |
1980年 | 20篇 |
1979年 | 26篇 |
1978年 | 18篇 |
1977年 | 19篇 |
1976年 | 22篇 |
1975年 | 16篇 |
1974年 | 8篇 |
1973年 | 7篇 |
1972年 | 9篇 |
1969年 | 8篇 |
排序方式: 共有1434条查询结果,搜索用时 31 毫秒
21.
Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains 总被引:6,自引:2,他引:6
Flint J; Bates GP; Clark K; Dorman A; Willingham D; Roe BA; Micklem G; Higgs DR; Louis EJ 《Human molecular genetics》1997,6(8):1305-1313
We have sequenced and compared DNA from the ends of three human
chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are
subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub-
domains with entirely different patterns of homology to other chromosome
ends. The distal regions contain numerous, short (<2 kb) segments of
interrupted homology to many other human telomeric regions. The proximal
regions show much longer (approximately 10-40 kb) uninterrupted homology to
a few chromosome ends. A comparison of all yeast subtelomeric regions
indicates that they too are subdivided by degenerate TTAGGG repeats into
distal and proximal sub-domains with similarly different patterns of
identity to other non-homologous chromosome ends. Sequence comparisons
indicate that the distal and proximal sub-domains do not interact with each
other and that they interact quite differently with the corresponding
regions on other, non- homologous, chromosomes. These findings suggest that
the degenerate TTAGGG repeats identify a previously unrecognized,
evolutionarily conserved boundary between remarkably different subtelomeric
domains.
相似文献
22.
23.
Induction of B cell apoptosis by co-cross-linking CD23 and sIg involves aberrant regulation of c-myc and is inhibited by bcl-2 总被引:2,自引:0,他引:2
Campbell KA; Studer EJ; Kilmon MA; Lees A; Finkelman F; Conrad DH 《International immunology》1997,9(8):1131-1140
A novel system to study the effects of co-cross-linking CD23/FceRII and sIg
on murine B lymphocytes utilizes a highly multivalent form of anti- Ig
prepared by covalently linking anti-Ig antibodies to a DNP-dextran
backbone. CD23-sIg co-cross-linking is accomplished by the addition of
DNP-specific monoclonal IgE. Previous studies demonstrated that co-
cross-linking CD23 and sIg significantly inhibited mouse B cell
proliferation, especially at high doses of the multivalent anti-Ig.
Interestingly, examination of early activation signals reveals no
difference in B cells subjected to co-cross-linking conditions as compared
to B cells activated with anti-Ig alone. Total cellular protein tyrosine
phosphorylation levels are unchanged by co-cross- linking. Analysis of B
cell mRNA reveals that co-cross-linking the receptors does not alter the
expression levels of ornithine decarboxylase 8 h after stimulation as
compared to the controls. In contrast, levels of the proto-oncogene c-myc
were significantly elevated 1 h after inducing B cell activation under
co-cross-linking conditions. However, it remains unclear whether this
aberrant c-myc regulation plays any role in inducing apoptosis. In
addition, on day 3 after stimulation, the co-cross-linking of CD23 and sIg
resulted in the formation of apoptotic B cells, determined by both
photomicroscopy of the B cell cultures and FACS analysis of B cell nuclei.
B cells obtained from bcl-2 transgenic mice proliferated as well as
controls, and failed to undergo apoptosis when CD23 and sIg were
co-cross-linked on their surface. These studies indicate that
co-cross-linking of CD23 with B cell sIg inhibits B cell proliferation by a
mechanism that is distinct from that seen by co-cross-linking of the Fc
gamma RII and sIg. In addition, these results suggest a means by which
antigen- specific IgE can down-regulate additional B cell activation and
IgE synthesis.
相似文献
24.
Canfield MC; Tamarappoo BK; Moses AM; Verkman AS; Holtzman EJ 《Human molecular genetics》1997,6(11):1865-1871
Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused
most often by mutations in the vasopressin V2 receptor (AVPR2). We studied
a family which included a female patient with NDI with symptoms dating from
infancy. The patient responded to large doses of desmopressin (dDAVP) which
decreased urine volume from 10 to 4 I/day. Neither the parents nor the
three sisters were polyuric. The patient was found to be a compound
heterozygote for two novel recessive point mutations in the aquaporin-2
(AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is
the site for inhibition of water permeation by mercurial compounds and is
located near to the NPA motif conserved in all aquaporins. Osmotic water
permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2
was not increased over water control, while expression of L22V cRNA
increased the Pf to approximately 60% of that for wild-type AQP2.
Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the
function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO
cells showed that the C181W mutant had an endoplasmic reticulum-like
intracellular distribution, whereas L22V and wild-type AQP2 showed endosome
and plasma membrane staining. Water permeability assays showed a high Pf in
cells expressing wild-type and L22V AQP2. This study indicates that AQP2
mutations can confer partially responsive NDI.
相似文献
25.
C-reactive protein (CRP) was assessed in pediatric serum samples using different commercial latex reagents, which were analyzed for species origin of the coating antibodies, homogeneity and density of the latex particles, and prozone agglutinating capacity. All reagents correctly agglutinated the positive and negative control sera. The antibodies coating the particles differed with regard to species origin: one was coated with rabbit, one with horse and goat, one with horse, goat, rabbit and swine, while the reference reagent had horse, goat and rabbit antibodies.Only the monospecies specific antibody-coated latex showed obvious prozoning; this reagent also had the smallest and most homogenous latex particles and showed the most clear-cut reactions. False agglutination was observed at 7–26% according to quantitation with the spot immunoprecipitate assay, which compared favorably with radial immunodiffusion measurements. The lowest percentage of false readings was noted for the rabbit antibody-coated particles; the highest for the reagent with particles coated using antibodies from 4 different species.No reagent had satisfactory precision for the low positive sera between 10 and 40 mg CRP/1. 相似文献
26.
Summary Thirty-two patients with common variable immunodeficiency (CVID) and two patients with IgA and IgG subclass deficiency received a total of 1,040 intravenous (i.v.) infusions during 60 patient years with 7,575 g of a new immunoglobulin (Ig) preparation. The content of prekallikrein activators and the anti-complementary activity in the tested Ig preparation was low and, in comparison to seven other commercial i.v. Igs, so was the proportion of IgG polymers and fragments. The IgA content was always 0.02 g/l, often <0.004 g/l, and it was possible to continuously give the Ig prophylactically to four patients with anti-IgA antibodies, i.e. three with CVID and one with combined IgA-IgG2 deficiency. Adverse reactions were only noted in 4.7% of the 1,040 infusions and in 12 out of the 34 patients. None of the reactions were of the anaphylactic type, but two patients had moderate reactions and one had anuria, probably not caused by the Ig. A simultaneous infection seemed to increase the risk of phlogistic reactions, as five out of six patients who reacted with temperature rise and chills had a simultaneous upper respiratory tract infection. A substudy of various dosage schedules was performed with 11 patients receiving 203 infusions over 10.8 patient years. On 25 mg/kg/week of Ig given i.v. every five weeks, a mean increase in the preinfusion serum IgG level of 0.3 g/l was observed, as compared to earlier i.m. prophylaxis with the same dose. Only 1/4 of the patients on 25 mg/kg/week every five or three weeks reached a preinfusion IgG level 3 g/l. On 50 mg/kg/week every two weeks, 4/4 CVID patients had preinfusion levels above 3 g/l with a mean preinfusion increase of 1.5 g/l over the start level. Finally, 100 mg/kg/week every three weeks gave 5/5 patients a preinfusion serum IgG level of >4 g/l with a mean rise of 3.6 g/l, as compared with the levels before the study. An association between decreasing preinfusion IgG serum levels and the presence of infection was noted on 13/17 occasions, while increasing IgG was seen in healthy periods on 14/14 observations.
1040 Infusionen mit einem nicht modifizierten Immunglobulin-Produkt, das bei Patienten mit Antikörpermangelsyndrom wenig Nebenwirkungen hervorruft
Zusammenfassung 32 Patienten mit gewöhnlichem variablen Immunglobulinmangel (CVID) und zwei Patienten mit fehlenden IgA- und IgG-Subklassen erhielten zusammen 1040 intravenöse (i.v.) Infusionen innerhalb von 60 Patientenjahren mit 7575 g einer neuen Immunglobulinpräparation (Ig). Der Gehalt an Prä-Kallikrein-Aktivatoren und die anti-komplementäre Aktivität in der getesteten Ig-Präparation war gering, verglichen mit sieben anderen kommerziell erhältlichen i.v. Immunglobulinen. Dasselbe gilt für den Anteil an IgG-Polymeren und -Fragmenten. Der IgA-Gehalt betrug immer 0,02 g/l, oft 0,004 g/l. Das Ig konnte vier Patienten mit IgA-Antikörpern, d. h. drei mit CVID und einem mit kombiniertem IgA-IgG-Mangel kontinuierlich verabreicht werden. Nur bei 4,7% der 1040 Infusionen und bei 12 der 34 Patienten wurden Nebenwirkungen beobachtet. Keine der Nebenwirkungen war vom anaphylaktischen Typ, aber zwei Patienten hatten mittelschwere Nebenwirkungen und einer eine Anurie, die wahrscheinlich nicht durch das Ig verursacht war. Das Risiko für phlogistische Reaktionen schien durch gleichzeitige Infektionen erhöht zu werden. Dies wurde bei fünf von sechs Patienten beobachtet, die bei Infektion der oberen Atemwege auf die Infusion mit Temperaturanstieg und Schüttelfrost reagierten. Bei 11 Patienten, die über 10,8 Patientenjahre 203 Infusionen erhielten, wurde eine Sonderstudie zu verschiedenen Dosierungen durchgeführt. Bei Infusion von 25 mg/kg/Woche i.v. alle fünf Wochen wurde ein mittlerer Anstieg der Serumspiegel vor Infusion gemessen, der um 0,3 g/l höher war als bei früherer i.m. Prophylaxe mit derselben Dosis. Nur bei 1/4 Patienten, die alle fünf oder drei Wochen 25 mg/kg/Woche erhielten, wurde ein IgG-Spiegel vor Infusion von 3 g/l erreicht. Bei Gabe von 50 mg/kg/Woche alle zwei Wochen hatten 4/4 CVID-Patienten vor Infusion Spiegel über 3 g/l, dabei stiegen die Spiegel vor Infusion um 1,5 g/l höher an als vor Therapiebeginn. Bei 100 mg/kg/Woche alle drei Wochen wiesen 5/5 Patienten ein Serum IgG von >4 g/l auf; der mittlere Anstieg gegenüber den Werten vor Studienbeginn betrug 3,6 g/l. Bei 13/17 Fällen wurde eine Assoziation von abnehmenden IgG-Serumspiegeln vor Infusion mit einer Infektion beobachtet; in gesunden Phasen waren bei 14/14 Beobachtungen Anstiege der IgG-Spiegel zu beobachten.相似文献
27.
Russell EJ; Geremia GK; Johnson CE; Huckman MS; Ramsey RG; Washburn-Bleck J; Turner DA; Norusis M 《Radiology》1987,165(3):609-617
Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes. 相似文献
28.
Brianna L. Doby Katie Ross-Driscoll Marion Shuck Matthew Wadsworth Christine M. Durand Raymond J. Lynch 《American journal of transplantation》2021,21(8):2646-2652
The Centers for Medicare and Medicaid Services announced changes to the Final Rule for organ procurement organizations (OPOs) in November 2020, after a 23-month period of public debate. One concern among transplant stakeholders was that public focus on OPO underperformance would harm deceased donation. Using CDC-WONDER data, we studied whether donation performance dropped during the era of public debate about OPO reform (December 2018–February 2020). Overall OPO performance as measured relative to cause, age, and location-consistent deaths rose by 12.3% in 2019, compared to a median annual change of 2.5% 2009–2019. Organ recoveries exceeded seasonally adjusted forecasts by 4.2% in the first half of 2019, by 8.1% following the Executive Order issuing a mandate for OPO metric reform, and by 14.1% between the Notice of Public Rule Making and the onset of COVID-19-related systemic disruptions. We describe changes in donor phenotype in the period of increased performance; improvement was greatest for older and donation after cardiac death (DCD) donors, and among decedents who did not have a drug-related mechanism of death. In summary, performance during an era of intense public debate and proposed regulatory changes yielded 692 additional donors over expectations, and no detriment to organ donation was observed. 相似文献
29.
Roux-Y Gastric Bypass: an effective anti-reflux procedure 总被引:1,自引:0,他引:1
Gastric limiting procedures have made an improvement in the lives of those patients in whom they have been successful. Not
only have there been marked improvements in diabetes, hypertension, and arthritis, but there have been a number of other ‘spin-offs’,
not the least of which is control of reflux esophagitis by totally eliminating the secretion of the parietal cell mass of
the stomach from rising into the esophagus. We compared a group of 100 obese patients with reflux esophagitis who underwent
Roux-Y gastric bypass (RYGBP) to a normalsized group of 23 patients on whom we had done Nissen fundoplications in the past.
Visick gradings I-II of 100% vs 87%, respectively, may indicate a superiority of RYGBP over the Nissen procedure. Although
the groups and time periods are too divergent to draw statistically significant conclusions, one can see that the RYGBP population
was apparently better served considering their cure of ‘heartburn’ and other reflux symptoms as well as their achievement
of sustained weight loss. 相似文献
30.
Serum protein profiles to identify head and neck cancer. 总被引:19,自引:0,他引:19
J Trad Wadsworth Kenneth D Somers Lisa H Cazares Gunjan Malik Bao-Ling Adam Brendan C Stack George L Wright O John Semmes 《Clinical cancer research》2004,10(5):1625-1632
PURPOSE: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management. The purpose of this study was to determine whether a new proteomic technology could correctly identify protein expression profiles for cancer in patient serum samples. EXPERIMENTAL DESIGN: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry ProteinChip system was used to screen for differentially expressed proteins in serum from 99 patients with HNSCC and 102 normal controls. Protein peak clustering and classification analyses of the surface-enhanced laser desorption/ionization spectral data were performed using the Biomarker Wizard and Biomarker Patterns software (version 3.0), respectively (Ciphergen Biosystems, Fremont, CA). RESULTS: Several proteins, with masses ranging from 2778 to 20800 Da, were differentially expressed between HNSCC and the healthy controls. The serum protein expression profiles were used to develop and train a classification and regression tree algorithm, which reliably achieved a sensitivity of 83.3% and a specificity of 100% in discriminating HNSCC from normal controls. CONCLUSIONS: We propose that this technique has potential for the development of a screening test for the detection of HNSCC. 相似文献