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排序方式: 共有4073条查询结果,搜索用时 15 毫秒
41.
Production of type-1 and type-2 cytokines by peripheral blood mononuclear cells of psoriatic patients. 总被引:6,自引:0,他引:6 下载免费PDF全文
N Mozzanica A Cattaneo D Trabattoni A F Finzi E Schmitt E Ferrario M Clerici G Vignati M L Villa 《Immunology》1995,86(3):422-426
We investigated the function of peripheral blood mononuclear cells (PBMC) in 16 patients with active psoriasis, in 15 patients with static psoriasis and in 27 healthy volunteers, by examining in vitro proliferation and antigen- and mitogen-stimulated production of interleukin-2 (IL-2) and IL-4. Plasma levels of the neuropeptide substance P were also determined. Defective alloantigen (ALLO)- and phytohaemagglutinin (PHA)-stimulated IL-2 production was detected in 42% and in 45% of psoriatic patients, respectively. The number of defective IL-2 responders was higher in static (60%) than in active (25%) psoriasis. The reduction of IL-2 responses in the former group was associated with an increase of IL-4 production. Thus PBMC of 66% of patients with static psoriasis but none of the patients with active psoriasis produced elevated amounts of PHA-stimulated IL-4. Variations of plasma substance P levels followed the same pattern of IL-4, being higher in static than in active psoriasis. These observations suggest a co-ordinated action of IL-4 and substance P as modulators of the clinical course of psoriasis. Our data show a possible correlation between the clinical evolution of psoriasis and the production of type-1 and type-2 cytokines, suggesting that the former may have a prominent role in the activation of psoriasis, while the latter may play a protective role. 相似文献
42.
Ashley Parrott Philip R. Khoury Amy R. Shikany Angela Lorts Chet R. Villa Erin M. Miller 《American journal of medical genetics. Part C, Seminars in medical genetics》2020,184(1):116-123
Pediatric cardiomyopathies can be caused by variants in genes encoding the sarcomere and cytoskeleton in cardiomyocytes. Variants are typically inherited in an autosomal dominant manner with variable expressivity. De novo variants have been reported, however their overall frequency is largely unknown. We sought to determine the rate of de novo, pathogenic and likely pathogenic (P/LP) variants in children with a diagnosis of hypertrophic, dilated, or restrictive cardiomyopathy (HCM, DCM, or RCM), and to compare disease outcomes between individuals with and without a de novo variant. A retrospective record review identified 126 individuals with HCM (55%), DCM (37%), or RCM (8%) ≤18 years of age who had genetic testing. Overall, 50 (40%) had positive genetic testing and 18% of P/LP variants occurred de novo. The rate of de novo variation in those with RCM (80%) was higher than in those with HCM (9%) or DCM (20%). There was evidence of germline mosaicism in one family with RCM. Individuals with de novo variants were more likely than those without to have a history of arrhythmia (p = .049), sudden cardiac arrest (p = .024), hospitalization (p = .041), and cardiac transplantation (p = .030). The likelihood of de novo variation and impact on family risk and screening should be integrated into genetic counseling. 相似文献
43.
Cell surface CD28 levels define four CD4+ T cell subsets: abnormal expression in rheumatoid arthritis 总被引:2,自引:0,他引:2
Salazar-Fontana LI Sanz E Mérida I Zea A Sanchez-Atrio A Villa L Martínez-A C de la Hera A Alvarez-Mon M 《Clinical immunology (Orlando, Fla.)》2001,99(2):253-265
CD28 is a costimulatory receptor expressed in most CD4(+) T cells. Despite the long-standing evidence for up- and downregulation of surface CD28 expression in vitro, and the key regulatory role assigned to the upregulation of CD28 counterreceptor [the CD152 (CTLA-4) molecule], in vivo CD28 induction has attracted little attention. We studied CD28 and CD152 expression and function in 33 rheumatoid arthritis (RA) patients, 20 clinically active and 13 inactive, and in 24 healthy donors. Four subsets of CD28(-), CD28(low), CD28(int), and CD28(high) peripheral blood human CD4(+) T cells were defined using three-color flow cytometry. The three CD28(+) subsets displayed a one-, two-, or threefold quantitative difference in their relative number of CD28 antibody binding sites, respectively (P < 0.01). RA patients, whether active or inactive, showed a distinct phenotype when compared to healthy donors: (i) the percentage of CD4(+)CD28(high) cells was increased twofold and the CD4(+)CD28(low) subset was reduced twofold (P < 0.01) and (ii) the CD4(+)CD28(high) cells from RA patients showed an in vivo activated phenotype, CD45RO(+)CD5(high)IL-2Ralpha(+) (P < 0.01). Active RA patients were different from inactive patients. They showed a twofold increase in mean CD28 expression (P < 0.05), whereas each of the CD28(+) subsets in the inactive RA patients showed reduced expression when compared to healthy donors. Notably, both active and inactive RA patients showed abnormal CD28 upregulation when T cells were activated in vitro with CD3 antibodies, but only inactive RA patients showed a hypoproliferative response to TCR/CD3 triggering when compared to healthy donors (P < 0.01). This defective proliferation was normalized by concurrent crosslinking with CD28 antibody. No differences were noted in the expression of CD152 or CD80, a CD28 and CD152 shared ligand. The disregulated in vivo expression of CD28 was related to the RA patients' disease activity and suggests that modulation of CD28 surface levels may be an additional mechanism to finely tune the delicate responsiveness/tolerance balance. 相似文献
44.
Allelic loss in human papillomavirus-positive and -negative vulvar squamous cell carcinomas 下载免费PDF全文
Pinto AP Lin MC Mutter GL Sun D Villa LL Crum CP 《The American journal of pathology》1999,154(4):1009-1015
Vulvar squamous cell carcinoma (VSCC) is a biologically and morphologically diverse disease, consisting of human papillomavirus (HPV)-positive and -negative tumors that differ in their morphological phenotypes and associated vulvar mucosal disorders. This study analyzed the frequencies of allelic loss (loss of heterozygosity (LOH)) in HPV-positive and -negative VSCCs to identify potential targets for the study of preinvasive diseases, to determine whether HPV status influenced patterns of LOH, and to determine whether these patterns differed from HPV-positive tumors of another genital site, cervical squamous cell carcinomas (CSCC). DNA extracted from microdissected archival sections of two index tumors, one each HPV negative and positive, was analyzed for LOH at 65 chromosomal loci. Loci scoring positive with either sample were included in an analysis of 14 additional cases that were also typed for HPV. Frequencies of LOH at loci were computed in a panel of HPV-positive and -negative VSCCs. Twenty-nine loci demonstrated LOH on the initial screen and were used to screen the remaining 14 tumors. High frequencies of LOH were identified, some of which were similar to a prior karyotypic study (3p, 5q, 8p, 10q, 15q, 18q, and 22q) and others of which had not previously been described in VSCC (1q, 2q, 8q, 10p, 11p, 11q, 17p, and 21q). With the exception of 5q and 10p, there were no significant associations between frequency of LOH and HPV status in VSCC. LOH at 3p and 11q were frequent in both VSCC and CSCC; however, allelic losses at several sites, including 5q, 8q, 17p, 21q, and 22q, were much more common in VSCC. VSCCs exhibit a broad range of allelic losses irrespective of HPV status, with high frequencies of LOH on certain chromosomal arms. This suggests that despite their differences in pathogenesis, both HPV-positive and -negative VSCCs share similarities in type and range of genetic losses during their evolution. Whether the different frequencies of LOH observed between VSCC and CSCC are real or reflect differences in stage and/or tumor size remains to be determined by further comparisons. The role of these altered genetic loci in the genesis of preinvasive vulvar mucosal lesions merits additional study. 相似文献
45.
Miguel Urioste María Luisa Martínez-Frías Eva Bermejo Nicols Jimnez Dolores Romero Carmen Nieto Amelia Villa 《American journal of medical genetics. Part A》1994,49(1):94-97
We report on a newborn infant with clinical and radiological manifestations of some type of short rib-polydactyly syndrome who died soon after birth. Chromosomal studies on peripheral blood lymphocytes and chondrocytes demonstrated an apparently balanced pericentric inversion of chromosome 4 (present in the mother also). This association may have occurred by chance but, if not, the chromosomal breakpoints could interrupt the gene responsible for short rib-polydactyly syndromes, or else be related to the mechanism of short rib-polydactyly syndromes. © 1994 Wiley-Liss, Inc. 相似文献
46.
47.
48.
Mahadevaiah SK; Odorisio T; Elliott DJ; Rattigan A; Szot M; Laval SH; Washburn LL; McCarrey JR; Cattanach BM; Lovell-Badge R; Burgoyne PS 《Human molecular genetics》1998,7(4):715-727
An RNA-binding motif (RBM) gene family has been identified on the human Y
chromosome that maps to the same deletion interval as the 'azoospermia
factor' (AZF). We have identified the homologous gene family (Rbm) on the
mouse Y with a view to investigating the proposal that this gene family
plays a role in spermatogenesis. At least 25 and probably >50 copies of
Rbm are present on the mouse Y chromosome short arm located between Sry and
the centromere. As in the human, a role in spermatogenesis is indicated by
a germ cell-specific pattern of expression in the testis, but there are
distinct differences in the pattern of expression between the two species.
Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are
female due to a position effect resulting in non-expression of Sry ;
sex-reversing such mice with an Sry transgene produces males with a high
incidence of abnormal sperm, making this the third deletion interval on the
mouse Y that affects some aspect of spermatogenesis. Most of the copies of
Rbm map to this deletion interval, and the Yd1males have markedly reduced
Rbm expression, suggesting that RBM deficiency may be responsible for, or
contribute to, the abnormal sperm development. In man, deletion of the
functional copies of RBM is associated with meiotic arrest rather than
sperm anomalies; however, the different effects of deletion are consistent
with the differences in expression between the two species.
相似文献
49.
Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity 总被引:13,自引:5,他引:13
Eichler EE; Budarf ML; Rocchi M; Deaven LL; Doggett NA; Baldini A; Nelson DL; Mohrenweiser HW 《Human molecular genetics》1997,6(7):991-1002
A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD)
locus of the X chromosome has duplicated to specific locations near the
pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11.
Comparative sequence analysis reveals 92-96% nucleotide identity,
indicating that the autosomal ALD paralogs arose relatively recently during
the course of higher primate evolution (5-10 million years ago). Analysis
of sequences flanking the duplication region identifies the presence of an
unusual GCTTTTTGC repeat which may be a sequence-specific integration site
for the process of pericentromeric- directed transposition. The breakpoint
sequence and phylogenetic analysis predict a two-step transposition model,
in which a duplication from Xq28 to pericentromeric 2p11 occurred once,
followed by a rapid distribution of a larger duplicon cassette among the
pericentromeric regions. In addition to facilitating more effective
mutation detection among ALD patients, these findings provide further
insight into the molecular basis underlying a pericentromeric-directed
mechanism for non- homologous interchromosomal exchange.
相似文献
50.
Queenan JT Jr; Veeck LL; Toner JP; Oehninger S; Muasher SJ 《Human reproduction (Oxford, England)》1997,12(7):1573-1576
In-vitro fertilization patients (n = 15) at risk of ovarian
hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day
of human chorionic gonadotrophin administration and 25 or more follicles of
intermediate or large size) underwent aspiration of all follicles and
cryopreservation of all fertilized oocytes at the pronuclear stage.
Patients were monitored for up to 2 weeks post- retrieval. Subsequent
transfer of cryopreserved-thawed embryos was performed in programmed cycles
using exogenous oestrogen and progesterone for endometrial preparation. Two
patients (13%) developed OHSS necessitating hospitalization and vaginal
aspiration of ascitic fluid. Two other patients (13%) developed moderate
OHSS requiring ascitic fluid vaginal aspiration in the office setting, with
dramatic improvement of the condition. Subsequent transfer of
cryopreserved- thawed embryos yielded a clinical pregnancy rate of 58% per
transfer and ongoing or delivery rates of 42 and 67% per transfer and per
patient respectively. By eliminating pregnancy potential with
cryopreservation of all prezygotes and examining the pregnancy potential
with subsequent cryopreserved-thawed transfers, it is concluded that OHSS
is reduced, but not eliminated for patients at risk. Subsequent transfer of
cryopreserved-thawed prezygotes in a programmed cycle with exogenous
steroids yields an excellent pregnancy rate.
相似文献