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21.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
22.
23.
Prolonged Replication of a Type 1 Vaccine-Derived Poliovirus in an Immunodeficient Patient 总被引:16,自引:5,他引:16
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Olen M. Kew Roland W. Sutter Baldev K. Nottay Michael J. McDonough D. Rebecca Prevots Linda Quick Mark A. Pallansch 《Journal of clinical microbiology》1998,36(10):2893-2899
VP1 sequences were determined for poliovirus type 1 isolates obtained over a 189-day period from a poliomyelitis patient with common variable immunodeficiency syndrome (a defect in antibody formation). The isolate from the first sample, taken 11 days after onset of paralysis, contained two poliovirus populations, differing from the Sabin 1 vaccine strain by ~10%, differing from diverse type 1 wild polioviruses by 19 to 24%, and differing from each other by 5.5% of nucleotides. Specimens taken after day 11 appeared to contain only one major poliovirus population. Evolution of VP1 sequences at synonymous third-codon positions occurred at an overall rate of ~3.4% per year over the 189-day period. Assuming this rate to be constant throughout the period of infection, the infection was calculated to have started ~9.3 years earlier. This estimate is about the time (6.9 years earlier) the patient received his last oral poliovirus vaccine dose, approximately 2 years before the diagnosis of immunodeficiency. These findings may have important implications for the strategy to eliminate poliovirus immunization after global polio eradication. 相似文献
24.
Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture 总被引:3,自引:1,他引:3
We have recently shown using dansyl-L-lysine exclusion studies that the
release of human chorionic gonadotrophin (HCG) in conjunction with L-
lactate dehydrogenase (LDH) from first trimester villi during organ culture
is symptomatic of syncytiotrophoblast degeneration. The purpose of this
study was to examine chorionic villi at the ultrastructural level in order
to determine events occurring during organ culture. The tissue was sampled
after 0, 24, 48 and 120 h in culture and processed for electron microscopy.
In addition to confirming the previously recorded syncytial degeneration,
the electron micrographs showed clearly the generation of a new
syncytiotrophoblast layer. The new layer, derived from differentiating
cytotrophoblast cells, was largely formed by 48 h and was maintained for at
least 120 h in culture. This study demonstrates a model which provides an
opportunity to study the differentiation of cytotrophoblast cells whilst
they retain their anatomical relationships within the villous structure.
相似文献
25.
26.
Fertilization, pregnancy and embryo implantation rates after ICSI in cases of obstructive and non-obstructive azoospermia 总被引:2,自引:0,他引:2
De Croo I Van der Elst J Everaert K De Sutter P Dhont M 《Human reproduction (Oxford, England)》2000,15(6):1383-1388
The aetiology of azoospermia can be grossly divided into obstructive and non-obstructive causes. Although in both cases testicular spermatozoa can be used to treat male fertility, it is not well established whether success rates following intracytoplasmic sperm injection (ICSI) are comparable. Therefore, a retrospective analysis of fertilization, pregnancy and embryo implantation rates was performed following ICSI with testicular spermatozoa in obstructive or non-obstructive azoospermia. In total, 193 ICSI cycles were carried out with freshly retrieved testicular spermatozoa; in 139 cases of obstructive and 54 cases of non-obstructive azoospermia. The fertilization rate after ICSI with testicular spermatozoa in non-obstructive azoospermia was significantly lower than in obstructive azoospermia (67.8% versus 74.5%; P = 0.0167). Within the non-obstructive group, the fertilization rate in the group of maturation arrest (47.0%) was significantly lower than in case of Sertoli cell-only (SCO) syndrome (71.2%) or germ cell hypoplasia (79. 5%). Embryo quality on day 2 after ICSI was similar for all groups. Pregnancy rates per transfer between obstructive (36.8%) and non-obstructive groups (36.7%) were similar. In cases of maturation arrest the pregnancy rate per transfer was lowest (20.0%) although not significantly different from SCO syndrome or hypoplasia groups. Embryo implantation rates were not different between the obstructive (19.6%) and non-obstructive groups (25.8%), and were lowest in cases of germ cell hypoplasia (15.8%). This retrospective analysis shows that although fertilization rate after ICSI with testicular spermatozoa in non-obstructive azoospermia is significantly lower than in obstructive azoospermia, pregnancy and embryo implantation rates are similar. 相似文献
27.
28.
Sperm plasma membrane damage prior to intracytoplasmic sperm injection: a necessary condition for sperm nucleus decondensation 总被引:2,自引:5,他引:2
Dozortsev D.; Rybouchkin A.; De Sutter P.; Dhont M. 《Human reproduction (Oxford, England)》1995,10(11):2960-2964
In the present study we investigated the relevance of spermimmobilization prior to intracytoplasmic sperm injection (ICSI)in the fertilization process. Using supravital staining of thespermatozoa with eosin and studying sperm decondensation with2 mM dithiothreitol (DTT) in conditions imitating sperm handlingduring ICSI, we demonstrated that immobilization of the spermatozoonby squeezing its tail between the glass pipette and the bottomof the dish damages the sperm plasma membrane. Polyvinylpyrrolidone(PVP), which is usually present in the drop with the spermatozoonto facilitate its handling, was found to impede the access ofboth eosin and DTT to the sperm nucleus. We conclude that (i)sperm immobilization prior to ICSI damages the sperm plasmamembrane, that (ii) this damage is sufficient for thiol-reducingagents to gain access to the sperm nucleus, and finally that(iii) PVP possibly interferes with sperm nucleus decondensation. 相似文献
29.
Fertilization, pregnancy and embryo implantation rates after ICSI with fresh or frozen-thawed testicular spermatozoa 总被引:2,自引:1,他引:2
De Croo I; Van der Elst J; Everaert K; De Sutter P; Dhont M 《Human reproduction (Oxford, England)》1998,13(7):1893-1897
This study aimed to determine whether fertilization and implantation rates
after intracytoplasmic sperm injection (ICSI) with fresh or frozen-thawed
testicular spermatozoa were comparable. Between 1 January 1996 and 31
December 1996, 65 ICSI cycles with testicular spermatozoa and 35 cycles
with frozen-thawed testicular spermatozoa were carried out. In 50 out of 65
ICSI cycles, testicular spermatozoa could be retrieved and in 34 out of 35
cycles carried out with frozen-thawed testicular spermatozoa, motile
spermatozoa could be recovered. The fertilization rate after ICSI with
frozen-thawed testicular spermatozoa was significantly lower (71.1%; P <
or = 0.008) than with fresh testicular spermatozoa (79.3%). The pregnancy
rate was similar for both groups (38.2 and 26.5 %). The implantation rate
per transferred embryo, however, was significantly lower in the
frozen-thawed rather than in the fresh testicular sperm group (9.1 versus
24.6%; P = 0.001). The live birth rate per transferred embryo was also
higher in the group in which fresh testicular spermatozoa were used (18.8
versus 7.9% P = 0.043). This retrospective study shows that is possible to
achieve a high fertilization rate after ICSI with both fresh and
frozen-thawed testicular spermatozoa but implantation and live birth rates
per transferred embryo, however, are significantly lower after ICSI with
frozen-thawed than with fresh testicular spermatozoa.
相似文献
30.
A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region 总被引:10,自引:0,他引:10
Akarsu AN; Turacli ME; Aktan SG; Barsoum-Homsy M; Chevrette L; Sayli BS; Sarfarazi M 《Human molecular genetics》1996,5(8):1199-1203
Primary congenital glaucoma (gene symbol: GLC3) is an ocular disorder that
occurs for 0.01-0.04% of blind people. In the majority of familial cases
reported so far, this condition is inherited as an autosomal recessive
trait. We have recently used a group of 17 GLC3 families with a minimum of
two affected offspring and consanguinity in most of the parental generation
and mapped the first GLC3 locus (GLC3A) to the 2p21 region. Six families
did not show any linkage to the GLC3A locus and thus provided evidence for
genetic heterogeneity of this disorder. A total of eight families unlinked
to the 2p21 region were used to search for the chromosomal location of the
second GLC3 locus. Herein, we describe mapping of a new locus (designated
GLC3B) for primary congenital glaucoma to the short arm of chromosome 1
(1p36.2-36.1) that is situated centromeric to the neuroblastoma and
Charcot-Marie-Tooth type 2A (CMT2A) loci. A total of 17 DNA markers were
genotyped from this region of chromosome 1. Four families showed no
recombination with the two markers D1S2834 and D1S402 with a maximum lod
score of 4.510 and 4.157 respectively. Pairwise and multipoint linkage
analysis and inspection of the haplotypes revealed that the remaining four
families are not linked to this part of chromosome 1, thus providing
further evidence that at least one more locus for the autosomal recessive
form of GLC3 must exist in the genome. Based on the recombination events,
the overall linkage map of this region is: tel-D1S1192-D1S1635-D1S1193 -
(D1S1597/-D1S489/D1S228)- [GLC3B/D1S2834/D1S402] - (D1S1176/D1S507/D1S407)
- D1S2728-(MFAP2/D1S170) - D1S1368 - D1S436- D1S1592-cen.
相似文献