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排序方式: 共有2348条查询结果,搜索用时 15 毫秒
991.
Kjeld?P?van Houwelingen Boukje?AC?van DijkEmail author Christina?A?Hulsbergen-van de Kaa Leo?J?Schouten Hanneke?JM?Gorissen Jack?A?Schalken Piet?A?van den Brandt Egbert?Oosterwijk 《BMC cancer》2005,5(1):57
Background
Biallelic von Hippel-Lindau (VHL) gene defects, a rate-limiting event in the carcinogenesis, occur in approximately 75% of sporadic clear-cell Renal Cell Carcinoma (RCC). We studied the VHL mutation status in a large population-based case group. 相似文献992.
Bone Mineral Density Increases in Trans Persons After 1 Year of Hormonal Treatment: A Multicenter Prospective Observational Study 下载免费PDF全文
Chantal M Wiepjes Mariska C Vlot Maartje Klaver Nienke M Nota Christel JM de Blok Renate T de Jongh Paul Lips Annemieke C Heijboer Alessandra D Fisher Thomas Schreiner Guy T'Sjoen Martin den Heijer 《Journal of bone and mineral research》2017,32(6):1252-1260
Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross‐sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first‐year effects of CHT on BMD in transgender persons. A total of 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol; transmen received transdermal or intramuscular testosterone. A dual‐energy X‐ray absorptiometry (DXA) was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after 1 year of CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval [CI] 3.20 to 4.13%, p < 0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p < 0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p < 0.001) BMD was found. In transmen, TH BMD increased after 1 year of CHT (+1.04%, 95% CI 0.64 to 1.44%, p < 0.001). No changes were observed in FN BMD (–0.46%, 95% CI –1.07 to 0.16%, p = 0.144). The increase in LS BMD was larger in transmen aged ≥50 years (+4.32%, 95% CI 2.28 to 6.36%, p = 0.001) compared with transmen aged <50 years (+0.68%, 95% CI 0.19 to 1.17%, p = 0.007). In conclusion, BMD increased in transgender persons after 1 year of CHT. In transmen of postmenopausal age, the LS BMD increased more than in younger transmen, which may lead to the hypothesis that the increase in BMD in transmen is the result of the aromatization of testosterone to estradiol. © 2017 American Society for Bone and Mineral Research. 相似文献
993.
Bourgeois P; Bolcato-Bellemin AL; Danse JM; Bloch-Zupan A; Yoshiba K; Stoetzel C; Perrin-Schmitt F 《Human molecular genetics》1998,7(6):945-957
Most targeted gene mutations are recessive and analyses of gene function
often focus on homozygous mutant phenotypes. Here we describe parts of the
expression pattern of M-twist in the head of developing wild-type mice and
present our analysis of the phenotype of heterozygous twist- null animals
at around birth and in adults. A number of twist -null heterozygous mice
present skull and limb defects and, in addition, we observed other
malformations, such as defects in middle ear formation and the xyphoid
process. Our study is of interest to understand bone formation and the role
of M-twist during this process, as within the same animal growth of some
bones can be accelerated while for others it can be delayed. Moreover, we
show here that expressivity of the mouse mutant heterozygous phenotype is
dependent on the genetic background. This information might also be helpful
for clinicians, since molecular defects affecting one allele of the human
H-twist ( TWIST ) gene were identified in patients affected with
Saethre-Chotzen syndrome (SCS). Expressivity of this syndrome is variable,
although most patients present craniofacial and limb malformations
resembling those seen in mutant mice. Thus the mutant mouse twist -null
strain might be a useful animal model for SCS. The twist -null mutant mouse
model, combined with other mutant mouse strains, might also help in an
understanding of the etiology of morphological abnormalities that appear in
human patients affected by other syndromes.
相似文献
994.
Sliwinski A Stanic D Finkelstein DI Ilic M West JM Dooley PC 《Journal of muscle research and cell motility》2005,26(2-3):149-155
It is well established that mammalian skeletal muscles exhibit a considerable degree of plasticity and one of the main determining
factors of this plasticity is the activity pattern and duration of motoneurone discharge. Lesions to the right substantia
nigra pars compacta (SNpc) of six adult rats were made to determine whether altered output from the SNpc ultimately leads
to a change in the expression of proteins in contralateral skeletal muscles. After 4 months, altered motor performance was
identified by the administration of amphetamine. After 7 months, 30–70% of dopaminergic cells in the SNpc had been destroyed.
The protein content of muscles was then quantified from densitometric scans of gels, and expressed as a % of the amount of
actin (the protein used as a reference in this study). The lesion affected the expression of different protein isoforms in
the fast- and slow-twitch muscles. In slow-twitch soleus muscles, the lesion decreased the proportion of α-tropomyosin and
increased the proportion of β-tropomyosin. In the fast-twitch extensor digitorum longus muscles, the lesion increased the
proportion of the fast isoform of troponin-T1f, and decreased the proportions of the two isoforms of myosin light chain. This study establishes a connection between the
chronic effects of a lesion to the SNpc, with a loss of dopaminergic neurones, impaired motor performance, and altered expression
of proteins in skeletal muscle. The implication of these results is that the altered motor function observed in Parkinson’s
disease may be associated with alterations to the expression of skeletal muscle proteins.
Supported by grants from NH & MRC (DF) and Faculty of Health Sciences, LaTrobe University (PD). 相似文献
995.
Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant 总被引:7,自引:3,他引:7
Sherrington R; Froelich S; Sorbi S; Campion D; Chi H; Rogaeva EA; Levesque G; Rogaev EI; Lin C; Liang Y; Ikeda M; Mar L; Brice A; Agid Y; Percy ME; Clerget- Darpoux F; Piacentini S; Marcon G; Nacmias B; Amaducci L; Frebourg T; Lannfelt L; Rommens JM; St George-Hyslop PH 《Human molecular genetics》1996,5(7):985-988
Missense mutations in the presenilin 2 (PS-2) gene on chromosome 1 were
sought by direct nucleotide sequence analysis of the open reading frame of
60 pedigrees with familial Alzheimer's disease (FAD). In the majority of
these pedigrees, PS-1 and beta-amyloid precursor protein (beta APP) gene
mutations had been excluded. While no additional PS-2 pathogenic mutations
were detected, four silent nucleotide substitutions and alternative
splicing of nucleotides 1338-1340 (Glu325) were observed. Analysis of
additional members of a pedigree known to segregate a Met239Val mutation in
PS-2 revealed that the age of onset of symptoms is highly variable (range
45-88 years). This variability is not attributable to differences in ApoE
genotypes. These results suggest (i) that, in contrast to mutations in
PS-1, mutations in PS-2 are a relatively rare cause of FAD; (ii) that other
genetic or environmental factor modify the AD phenotype associated with
PS-2 mutations; and (iii) that still other FAD susceptibility genes remain
to be identified.
相似文献
996.
Afina W Lemstra Jacqueline CM Groen in't Woud Jeroen JM Hoozemans Elise S van Haastert Annemiek JM Rozemuller Piet Eikelenboom Willem A van Gool 《Journal of neuroinflammation》2007,4(1):4-8
Background
infection induces an acute phase response that is accompanied by non-specific symptoms collectively named sickness behavior. Recent observations suggest that microglial cells play a role in mediating behavioral changes in systemic infections. In animal models for sepsis it has been shown that after inducing lipopolysaccharide, LPS, microglia in the brain were activated. The aim of this study was to investigate whether activation of microglia can be detected in patients who died of sepsis. 相似文献997.
Lina Berkun Mordechai Slae Hagar Mor‐Shaked Benjamin Koplewitz Smadar Eventov‐Friedman Tamar Harel 《American journal of medical genetics. Part A》2019,179(12):2454-2458
Cases with multiple molecular diagnoses are challenging to diagnose clinically, yet may be resolved by unbiased exome sequencing analysis. We report an infant with developmental delay, severe growth delay, dysmorphic features, and multiple congenital anomalies including retinal coloboma, congenital pyloric stenosis, and circumferential skin creases. Exome sequencing identified a homozygous missense variant in MAPRE2 and a homozygous stopgain (nonsense) variant in CDON. Variants in MAPRE2, encoding a regulator of microtubule dynamics, lead to congenital symmetric circumferential skin creases type 2, with associated dysmorphism, small growth parameters, and congenital cardiac and genital anomalies. Monoallelic variants in CDON, encoding a coreceptor for sonic hedgehog, have been associated with autosomal dominant pituitary stalk interruption syndrome and holoprosencephaly. Cdon?/? mice have multiple eye defects including coloboma, consistent with the observed human phenotype. Thus, the complex phenotypic presentation of the infant may potentially be attributed to a dual molecular diagnosis. Furthermore, we present CDON as a candidate gene for coloboma formation in addition to the known holoprosencephaly phenotype, and propose to expand the allelic spectrum of CDON to variants associated with autosomal recessive inheritance in addition to dominant inheritance. 相似文献
998.
999.
First trimester maternal serum concentrations of fetal antigen 2 in normal pregnancies and those affected by trisomy 21 总被引:1,自引:0,他引:1
Price KM; Van Lith JM; Silman R; Mantingh A; Grudzinskas JG 《Human reproduction (Oxford, England)》1998,13(6):1706-1708
Serum concentrations of fetal antigen 2 (FA-2), the amino-propeptide of the
alpha1 chain of collagen type I, were measured in peripheral blood from
women with normal (n = 234) and trisomy 21 affected (n = 14) pregnancies
between 9 and 11 weeks gestation. Serum FA-2 concentrations were seen to be
stable throughout this period, and though raised FA-2 concentrations were
seen at the 10th week of gestation, a statistically significant difference
between normal and trisomy 21 affected pregnancies was not found overall.
Therefore it seems unlikely that FA- 2 has a role in first trimester
screening for trisomy 21, despite the fact that significantly higher FA-2
concentrations in trisomy 21 and significantly lower concentrations in
trisomy 18 had been previously demonstrated in amniotic fluid in the second
trimester.
相似文献
1000.
Skeletal muscle is an attractive target for somatic gene transfer of both
acquired and inherited disorders. Direct injection of adenoviral vectors in
the skeletal muscle leads to recombinant gene expression in a large number
of muscle fibers. Transgene expression has been transient in most organs
and associated with substantial inflammation when experiments are performed
in adult immune competent mice. In this report, we utilize a variety of in
vivo and in vitro models of T and B cell function to characterize the
nature of the immune response to adenoviral vectors injected into murine
skeletal muscle. Cellular immunity dependent on CD4+ and CD8+ T cells
contributes to the loss of recombinant gene expression and the development
of localized inflammation. Antigen specific activation of T cells occurs to
both viral proteins and the reporter gene beta-galactosidase. Systemic
levels of neutralizing antibody to the capsid proteins of the vector are
also generated. Destructive immune responses responsible for loss of
transgene expression are largely directed against beta-galactosidase in
that transgene expression was stable when beta-galactosidase was eliminated
as a neoantigen in mice transgenic for lacZ. A strategy to prevent the
cellular and humoral immunity to this therapy was developed based on
transiently ablating CD4+ T cell activation at the time of vector delivery.
Encouraging results were obtained when vector was administered with one of
several immune modulating agents including cyclophosphamide, mAb to CD4+
cells, and mAb to CD40 ligand. These studies indicate that cellular and
humoral immune responses are elicited in the context of gene therapy
directed to skeletal muscle with adenoviral vectors. Transient ablation of
CD4+ T cell activation prevents the effects responses of the CD8+ T and B
cells.
相似文献