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71.
Demuth I Wlodarski M Tipping AJ Morgan NV de Winter JP Thiel M Gräsl S Schindler D D'Andrea AD Altay C Kayserili H Zatterale A Kunze J Ebell W Mathew CG Joenje H Sperling K Digweed M 《European journal of human genetics : EJHG》2000,8(11):861-868
FANCG was the third Faconi anaemia gene identified and proved to be identical to the previously cloned XRCC9 gene. We present the pathogenic mutations and sequence variants we have so far identified in a panel of FA-G patients. Mutation screening was performed by PCR, single strand conformational polymorphism analysis and protein truncation tests. Altogether 18 mutations have been determined in 20 families - 97% of all expected mutant alleles. All mutation types have been found, with the exception of large deletions, the large majority is predicted to lead to shortened proteins. One stop codon mutation, E105X, has been found in several German patients and this founder mutation accounts for 44% of the mutant FANCG alleles in German FA-G patients. Comparison of clinical phenotypes shows that patients homozygous for this mutation have an earlier onset of the haematological disorder than most other FA-G patients. The mouse Fancg sequence was established in order to evaluate missense mutations. A putative missense mutation, L71P, in a possible leucine zipper motif may affect FANCG binding of FANCA and seems to be associated with a milder clinical phenotype. 相似文献
72.
Gonadotrophin-releasing hormone agonist dose-dependency of pituitary desensitization during controlled ovarian hyperstimulation in IVF 总被引:2,自引:2,他引:2
Janssens RM; Vermeiden JP; Lambalk CB; Schats R; Schoemaker J 《Human reproduction (Oxford, England)》1998,13(9):2386-2391
The aim of this study was to find the minimal effective daily s.c. dose of
the gonadotrophin-releasing hormone (GnRH) agonist, triptorelin acetate,
that suppresses the GnRH-induced release of luteinizing hormone (LH) at
time of human chorionic gonadotrophin (HCG) injection and thereby prevents
spontaneous LH surges during in-vitro fertilization (IVF) stimulation
cycles. Therefore, a double-blind, prospective and randomized titration
study was performed. A total of 48 IVF patients were divided into four
groups of 12 patients. Each group received a different dose of triptorelin
acetate, namely 5, 15, 50 or 100 microg s.c. daily. Standard ovarian
stimulation was carried out using urinary follicle stimulating hormone
(FSH) preparations. A 500 microg GnRH test was performed 90 min before the
HCG injection in order to measure the degree of pituitary desensitization.
Spontaneous LH surges were not detected in any of the groups, although
three patients in the 5 microg group had ovulated at the time of ovum
retrieval. The pituitary LH response to the GnRH test at time of HCG,
expressed as area under the curve (AUC), appeared to be dose-dependent.
Thus, a daily s.c. dose of 100 microg triptorelin acetate appears to be too
high, since adequate desensitization of the pituitary (i.e. no spontaneous
LH surge) can be achieved with doses as low as 15 and 50 microg.
相似文献
73.
B lymphocytes secreting IgG linked to latent transforming growth factor- beta prevent primary cytolytic T lymphocyte responses 总被引:3,自引:0,他引:3
B lymphocytes secreting IgG linked to latent transforming growth factor
(TGF)-beta (IgG-TGF-beta) prevent cytolytic T lymphocyte (CTL) responses to
unrelated antigens in mixed lymphocyte cultures (MLC) so long as resting
resident macrophages and functional Fc receptors are present. This was
shown using IgG-secreting plaque-forming cells (PFC) to sheep erythrocytes
(SRBC) obtained from popliteal lymph nodes of mice injected repeatedly in
foot pads with SRBC. Remarkably, as few as approximately 300 PFC prevented
CTL responses of 5 x 10(5) normal syngeneic spleen cells in MLC.
Supranatants of short-term cultures of PFC also prevented CTL responses,
and suppression was prevented by eliminating or dissociating IgG and
TGF-beta present in supranatants or by antibody against active TGF-beta.
Furthermore, the latency- associated peptide of latent TGF-beta was
detected in approximately 10% of foci of IgG captured from single PFC,
indicating that at least some B lymphocytes secrete IgG-TGF-beta as a
complex. Resting resident macrophages (which do not produce latent
TGF-beta) and functional Fc receptors were required for suppression,
consistent with idea that IgG- TGF-beta is taken up through Fc receptors
for IgG and that active TGF- beta, cleaved from latent TGF-beta of the
complex, is delivered directly to potentially responding CTL. If CTL
responses in man are similarly regulated by B lymphocytes, then an ongoing
B cell response in patients with chronic viral infections or bearing
immunogenic cancers may prevent effective therapeutic vaccination.
相似文献
74.
Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3 总被引:4,自引:2,他引:4
Cruts Marc; Backhovens Hubert; Wang Sheng-Yue; Van Gassen Geert; Theuns Jessie; De Jonghe Chris; Wehnert Anita; De Voecht Joke; De Winter Goedele; Cras Patrick; Bruyland Marc; Datson Nicole; Weissenbach Jean; Dunnen Johan T.den; Martin Jean-Jaques; Hendriks Lydia; Van Broeckhoven Christine 《Human molecular genetics》1995,4(12):2363-2371
Genetic linkage studies have indicated that chromosome 14q24.3harbours a major locus for early-onset (onset age <65 years)Alzheimer's disease (AD3). Positional cloning efforts have identifieda novel gene S182 or presenilin 1 as the AD3 gene. We have mappedS182 in the AD3 candidate region between D14S277 and D14S284defined by genetic linkage studies in the two chromosome 14linked, early-onset AD families AD/A and AD/B. We have shownthat S182 is expressed in lymphoblasts and have determined thecomplete cDNA in both brain and lymphoblasts by RT-PCR sequencing.S182 is alternatively spliced in both brain and lymphoblastswithin a putative phosphorylation site located 5' in the codingregion. We identified two novel mutations, Ile143Thr and Gly384Alalocated in, respectively, the second transmembrane domain andin the sixth hydrophilic loop of the putative transmembranestructure of S182. As families AD/A and AD/B have a very similarAD phenotype our observation of two mutations in functionallydifferent domains suggest that onset age and severity of ADmay not be very helpful predictors of the location of putativeS182 mutations. 相似文献
75.
Unified theory regarding A/P and M/L balance in quiet stance 总被引:26,自引:0,他引:26
Winter D. A.; Prince F.; Frank J. S.; Powell C.; Zabjek K. F. 《Journal of neurophysiology》1996,75(6):2334-2343
76.
A child with sclerocornea, short limbs, short stature, and distinct facial appearance 总被引:1,自引:0,他引:1
We describe a boy with sclerocornea, short limbs, short stature and a distinct facial appearance. The resemblance to other reports of affected sibs suggests that this is a newly recognised, autosomal recessive syndrome. 相似文献
77.
Effect of ageing of serum on consumption of antibody by B1C-globulin determinants; evidence for circulating breakdown products in glomerulonephritis
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C. D. West Sara Winter Judith Forristal N. C. Davis 《Clinical and experimental immunology》1968,3(1):57-62
Changes in antibody consumption by the A and D determinants of β1C-globulin were found to increase as serum aged in vitro. Consumption by the A determinant was 1·6 times and by the D determinant, 2·5–3 times greater in aged serum than in fresh EDTA plasma. The most likely explanation for the increased consumption with ageing is steric changes occurring as the β1C molecule fragments into β1A and α2D, resulting in exposure of additional antibody combining sites. In specimens from patients with hypocomplementemic nephritis, the increase in consumption with ageing was less than in normal subjects. The data add to the evidence presented in earlier studies of the presence in vivo, in certain nephritics, of breakdown products of β1C-globulin. The most abundant breakdown product would be α2D-globulin. 相似文献
78.
Antibody-mediated protection against Brucella abortus in BALB/c mice at successive periods after infection: variation between virulent strain 2308 and attenuated vaccine strain 19. 总被引:2,自引:0,他引:2
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In BALB/c mice antibodies specific for the O polysaccharide (OPS) as well as T lymphocytes mediate protective immunity to Brucella abortus. We performed quantitative analyses of isotypes of OPS antibodies generated during primary infections, and tested the protective qualities of antisera at successive stages of infection against B. abortus strain 2308, representative of the wild type, and attenuated vaccine strain 19. IgM antibodies predominated during the first 3-4 weeks of infection. IgG3 antibodies increased slowly for the first 3 weeks but then rose rapidly and persisted at high levels (> 300 micrograms/ml). IgG1, IgG2a and IgG2b antibodies had increased slightly by week 4 and then remained at low to moderate levels (< 70 micrograms/ml). Week 2 serum pools (IgM high, IgG3 low or undetectable) transferred substantial protection against 2308 (> or = 1 log unit) which increased relatively little (to 1.2-1.5 log units) with later sera that were high in IgG antibodies. In contrast, week 2 sera conferred low levels of protection against 19 (< 0.6 log units), but protection was dramatically increased (to > or = 2.3 log units) with sera obtained 1 week later that had slightly increased IgG antibodies. Monoclonal IgM antibodies also provided better protection against 2308 than 19, while monoclonal IgG3 antibodies protected much better against 19. Strain 19 opsonized with antibodies taken at any stage of infection was killed within normal macrophages, whereas comparably opsonized 2308 underwent intracellular replication. Phagocytosis of 2308 was better than of 19 when brucellae were opsonized with either polyclonal IgM or IgG3 antibodies, and the difference between strains was more extreme following IgM opsonization. The data suggest an explanation for differences in the growth curves of 2308 and 19 in spleens of BALB/c mice. Higher numbers achieved by 19 at week 2 could result from extracellular replication owing to ineffectual opsonization by IgM antibodies, while the precipitous decline of 19 beginning at week 3 could be caused by the increase in more effective IgG3 opsonins that facilitate its rapid intracellular destruction. 相似文献
79.
W. Reardon S. P. McManus D. Summers R. M. Winter 《American journal of medical genetics. Part A》1993,47(5):633-636
Evidence for the location of the Saethre-Chotzen acrocephalosyndactyly mutation on 7p21–22 is based on genetic linkage studies in families segregating for this autosomal dominant disorder. Linkage studies were guided by several reports of chromosome deletions in this region giving rise to craniosynostosis and some other manifestations of Saethre-Chotzen syndrome. We report on a family where a father and daughter carry an apparently balanced t(7;10)(p21.2;q21.2) translocation (de novo in the father) and have the Saethre-Chotzen syndrome. These observations support the localization of the Saethre-Chotzen gene to 7p21.2. © 1993 Wiley-Liss, Inc. 相似文献
80.