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排序方式: 共有696条查询结果,搜索用时 31 毫秒
1.
A I D'hulst K R Bracke T Maes J L De Bleecker R A Pauwels G F Joos G G Brusselle 《The European respiratory journal》2006,28(1):102-112
Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease. 相似文献
2.
J. De Bleecker W. van Landegem L. Crevits J. De Reuck 《Acta neurologica Scandinavica》1992,85(2):150-153
A 23-year-old man suffered from palatal myoclonus for 2 years. It had appeared one week after a minor head trauma. MRI and basal cisternography revealed a localized atrophy of the left paramedian part of the medulla, encroached upon the left vertebral artery. Clonazepam treatment was beneficial. This particular case is discussed in relation to etiopathogenesis and other causes of palatal myoclonus. 相似文献
3.
A 49-year-old man presented with episodic hypothermia many years after sustaining a contusional brain injury. Brain magnetic resonance imaging demonstrated the destruction of the anterior parts of the corpus callosum without hypothalamic lesions. Nevertheless, delayed hypothalamic dysfunction at the neurotransmitter level is the probable pathophysiological key factor. Clomipramine treatment was beneficial. This case expands the spectrum of Shapiro's syndrome. 相似文献
4.
Mary ER O'Brien Janet Hardy Sylvia Tan Jackie Walling Brian Peters Sarah Hatty Eve Wiltshaw 《Cancer chemotherapy and pharmacology》1992,30(3):245-248
Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted. 相似文献
5.
S P Peters R S Tung M Chatham E R Bleecker L M Lichtenstein 《International archives of allergy and applied immunology》1985,76(4):344-349
Circulating human basophils contain histamine, a potent mediator of inflammation. Previous in vitro studies have shown that histamine 'releasability' in asthmatic subjects differs from normal subjects but have not evaluated possible differences in the immunopharmacological control of the release of this mediator which might account for these differences. The purpose of the present study was to examine the immunopharmacologic control of basophil histamine release in 14 asthmatics and 10 normal subjects who were characterized by pulmonary function tests, allergic status (skin tests and serum IgE levels) and nonspecific airways reactivity to methacholine and histamine. Basophils were stimulated with anti-IgE, and the inhibitory effects of the H2 agonist, dimaprit, and dibutyryl cyclic AMP (dbcAMP), as well as the enhancing properties of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and indomethacin on the modulation of histamine release, were investigated. Although no statistically significant differences were seen in the percent histamine release triggered by anti-IgE in these two groups, enhancement of histamine release by 5-HPETE was more consistent in the asthmatic subjects (10 of 10) than in control subjects (6 of 8). The percent increase in histamine release produced by 5-HPETE in asthmatic subjects averaged 3.9 +/- 1.3% using 0.03 micrograms anti-IgE/ml and 4.8 +/- 3.2% using 0.1 microgram anti-IgE/ml (p less than 0.002, Wilcoxon's signed rank test), and averaged 3.0 +/- 4.3 and 3.1 +/- 5.3%, respectively, in control subjects (p greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group 总被引:5,自引:0,他引:5
Haines JL; Terwedow HA; Burgess K; Pericak-Vance MA; Rimmler JB; Martin ER; Oksenberg JR; Lincoln R; Zhang DY; Banatao DR; Gatto N; Goodkin DE; Hauser SL 《Human molecular genetics》1998,7(8):1229-1234
Multiple sclerosis (MS) is a demyelinating autoimmune disease of the
central nervous system. While its etiology is not well understood, genetic
factors are clearly involved. Until recently, most genetic studies in MS
have been association studies using the case-control design testing
specific candidate genes and studying only sporadic cases. The only
consistently replicated finding has been an association with the HLA-DR2
allele within the major histocompatibility complex (MHC) on chromosome 6.
Using the genetic linkage design, however, evidence for and against linkage
of the MHC to MS has been found, fostering suggestions that sporadic and
familial MS have different etiologies. Most recently, two of four genomic
screens demonstrated linkage to the MHC, although specific allelic
associations were not tested. Here, a dataset of 98 multiplex families was
studied to test for an association to the HLA-DR2 allele in familial MS and
to determine if genetic linkage to the MHC was due solely to such an
association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta)
in the MHC demonstrated strong genetic linkage (parametric lod scores of
4.60, 2.20 and 1.24, respectively) and a specific association with the
HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results
by HLA-DR2 status showed that the linkage results were limited to families
segregating HLA-DR2 alleles. These results demonstrate that genetic linkage
to the MHC can be explained by the HLA-DR2 allelic association. They also
indicate that sporadic and familial MS share a common genetic
susceptibility. In addition, preliminary calculations suggest that the MHC
explains between 17 and 62% of the genetic etiology of MS. This
heterogeneity is also supported by the minority of families showing no
linkage or association with loci within the MHC.
相似文献
7.
8.
Koppelman GH Stine OC Xu J Howard TD Zheng SL Kauffman HF Bleecker ER Meyers DA Postma DS 《The Journal of allergy and clinical immunology》2002,109(3):498-506
BACKGROUND: Atopy is a phenotype associated with asthma that has a heritable component. However, the role of atopysusceptibility genes in the development and expression of asthma and allergic disorders is not understood. OBJECTIVE: We sought to study the familial aggregation and co-occurrence of atopic phenotypes within family members of patients with asthma and to identify chromosomal regions that may contain genes that regulate different atopic phenotypes. METHODS: In 200 families (n = 1174) ascertained through a proband with asthma, genome-wide screen and linkage analysis was performed for the following atopic phenotypes: (1) specific IgE to common aeroallergens (Phadiatop assay); (2) specific IgE to Der p 1; (3) positive skin test responses to house dust mite; (4) positive skin test responses to 1 or more of 16 allergens; and (5) peripheral blood eosinophils. Results were compared with the linkage results for total serum IgE levels. RESULTS: There was clear familial aggregation of atopy. A high total serum IgE level in combination with a positive Phadiatop result or a normal total IgE level in combination with a negative Phadiatop result was found in 56.1% of the probands and 66.9% of the offspring. Several chromosomal regions that showed evidence for linkage to an atopic phenotype (ie, 2q, 6p, 7q, and 13q) also showed evidence of linkage with total serum IgE (Xu et al. Am J Hum Genet 2000;67:1163-73). Specific regions of interest for atopic traits were also detected on chromosomes 11q, 17q, and 22q. CONCLUSIONS: Atopic phenotypes show familial aggregation, although family members may differ in expression of atopy. Specific chromosomal regions appear to be important in susceptibility to different phenotypes of atopic responsiveness. 相似文献
9.
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
10.
Possible health care professional-to-patient HIV transmission. Dentists' reactions to a Centers for Disease Control report. 总被引:1,自引:0,他引:1
On July 27, 1990, the Centers for Disease Control reported possible transmission of the human immunodeficiency virus (HIV) from a dentist to a patient as a result of patient care. We surveyed a random national probability sample of 300 dentists with a 26-item survey in August and September 1990 to assess reactions to the report (response rate, 59%). Respondents tended not to believe the report (mean was 3.2, median 3.0, where 1 indicated "do not believe" and 7 indicated "believe"). Our sample also tended to believe that transmission of HIV from dentists to patients was unlikely in the future (mean was 2.0, median 2.0, where 1 indicated "not at all likely" and 7 indicated "very likely"). Fifty-one percent of our sample recommended that dentists infected with HIV should discontinue practice, while 38% recommended continuing practice with changes in procedures. Seventy-four percent believed patients should be told if their dentist was infected with HIV. In summary, dentists doubted the possibility of dentist-to-patient transmission of HIV and did not believe the Centers for Disease Control case report, but they did believe infected dentists should refrain from clinical work or modify their practice. 相似文献